subject:(binding site)

North Carolina State University

1. Wang, Tianyuan. Identifying Transcription Factor Targets and Studying Human Complex Disease Genes.

Degree: PhD, Bioinformatics, 2009, North Carolina State University

URL: http://www.lib.ncsu.edu/resolver/1840.16/3628

► Transcription factors (TFs) have been characterized as mediators of human complex disease processes. The target genes of TFs also may be associated with disease. Identification… (more)

▼ Transcription factors (TFs) have been characterized as mediators of human complex disease processes. The target genes of TFs also may be associated with disease. Identification of potential TF targets could further our understanding of gene-gene interactions underlying complex disease. We focused on two TFs, USF1 and ZNF217, because of their biological importance, especially their known genetic association with coronary artery disease (CAD), and the availability of chromatin immunoprecipitation microarray (ChIP-chip) results. First, we used USF1 ChIP-chip data as a training dataset to develop and evaluate several kernel logistic regression prediction models. Our most accurate predictor significantly outperformed standard PWM-based prediction methods. This novel prediction method enables a more accurate and efficient genome-scale identification of USF1 binding and associated target genes. Second, the results from independent linkage and gene expression studies suggest that ZNF217 also may be a candidate gene for CAD. We further investigated the role of ZNF217 for CAD in three independent CAD samples with different phenotypes. Our association studies of ZNF217 identified three SNPs having consistent association with CAD in three samples. Aorta expression profiling indicated that the proportion of the aorta with raised lesions was also positively correlated to ZNF217 expression. The combined evidence suggests that ZNF217 is a novel susceptibility gene for CAD. Finally, we applied our previously developed TF binding site (TFBS) prediction method to ZNF217. The performance of the prediction models of ZNF217 and USF1 are very similar. We demonstrated that our TFBS prediction method can be extended to other TFs. In summary, the results of this dissertation research are (1) evaluation of two TFs, USF1 and ZNF217, as susceptibility factors for CAD; (2) development of a generalized method for TFBS prediction; (3) prediction of TFBSs and target genes of two TFs, and identification of SNPs within TFBSs. This research allows for the development of study design to access TF based interactions in genetic susceptibility to human complex disease. Advisors/Committee Members: Elizabeth R. Hauser, Committee Co-Chair (advisor), Jonathan M. Horowitz, Committee Member (advisor), David McK. Bird, Committee Member (advisor), Steffen Heber, Committee Co-Chair (advisor), Jeffrey L. Thorne, Committee Member (advisor).

Subjects/Keywords: binding site; prediction; transcription factor

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APA (6^th Edition):

Wang, T. (2009). Identifying Transcription Factor Targets and Studying Human Complex Disease Genes. (Doctoral Dissertation). North Carolina State University. Retrieved from http://www.lib.ncsu.edu/resolver/1840.16/3628

Chicago Manual of Style (16^th Edition):

Wang, Tianyuan. “Identifying Transcription Factor Targets and Studying Human Complex Disease Genes.” 2009. Doctoral Dissertation, North Carolina State University. Accessed February 27, 2021. http://www.lib.ncsu.edu/resolver/1840.16/3628.

MLA Handbook (7^th Edition):

Wang, Tianyuan. “Identifying Transcription Factor Targets and Studying Human Complex Disease Genes.” 2009. Web. 27 Feb 2021.

Vancouver:

Wang T. Identifying Transcription Factor Targets and Studying Human Complex Disease Genes. [Internet] [Doctoral dissertation]. North Carolina State University; 2009. [cited 2021 Feb 27]. Available from: http://www.lib.ncsu.edu/resolver/1840.16/3628.

Council of Science Editors:

Wang T. Identifying Transcription Factor Targets and Studying Human Complex Disease Genes. [Doctoral Dissertation]. North Carolina State University; 2009. Available from: http://www.lib.ncsu.edu/resolver/1840.16/3628

University of Missouri – Columbia

2. Byrne, Todd S. Structural interactions sites of matrix metalloproteinase-12 with collagen triple helix, micelles, and a natural product from green tea.

Degree: 2012, University of Missouri – Columbia

URL: http://hdl.handle.net/10355/33129

► Matrix metalloproteinase (MMP-12) is associated with many costly, life-threatening diseases, such as atherosclerosis, pulmonary emphysema, asthma, and multiple sclerosis. Therefore, macrophage secreted MMP-12 is likely… (more)

▼ Matrix metalloproteinase (MMP-12) is associated with many costly, life-threatening diseases, such as atherosclerosis, pulmonary emphysema, asthma, and multiple sclerosis. Therefore, macrophage secreted MMP-12 is likely found in many parts of the body likely interacting with extracellular components as have been shown and previously investigated by in vitro studies. MMP-12 is capable of cleaving elastin and may biologically cleave other extracellular components, such as collagen. This article seeks to investigate interactions of MMP-12 with a collagen-mimicking triple helical peptide (THP). The methods employed for this study involved paramagnetic relaxation enhancement (PRE). A THP paramagnetically labeled with the artificial amino acid TOAC was used to investigate the interaction between MMP-12 and a THP. This study aims to answer the question of how a THP binds to MMP-12. Preliminary structures of the complex presented here have converged. The THP binds to MMP-12 in a specific manner in one type of angle of inclination. Whereby, the orientations of the THP appear to have the N-terminus along the unprimed side of MMP-12. These results may also further hint at an exosite near the C2 calcium binding site on MMP-12. The inhibition of MMP-12 by a natural polyphenol, (-)-Epigallocatechin gallate (EGCG) was investigated. Also, structural information concerning the binding sites of EGCG to MMP-12 was obtained. The methods employed involve paramagnetic relaxation enhancement, inhibition of enzyme activity, and stability by urea denaturation. A paramagnetic ECG, an analog of EGCG, was generated by incubating briefly in the presence of peroxide and horse radish peroxidase. The radical was used in an attempt to characterize the interaction between EGCG and MMP-12. The initial NMR investigations involving paramagnetic relaxation enhancement (PRE) or/and NOE experiments with EGCG suggest two to three binding sites on MMP-12, including one near a calcium binding site. Inhibition of enzyme kinetics and denaturation melts were also carried out with MMP-12 in the presence of EGCG to better ascertain the most significant binding site of EGCG to MMP-12. The kinetic experiments indicate that inhibition appears to be non-competitive, and there is a calcium dependence for the EGCG inhibition of MMP-12. The calcium dependent inhibition suggests that the calcium site (C2 site or Ca 403) indicated in the PRE and NOE experiments could be the key site of allosteric inhibition of MMP-12 by EGCG. This study investigates the interaction of MMP-12 with dodecyl phosphatidylcholine (DPC) micelles and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) micelles. The composition of the micelles has been varied. For example, DPC/CHAPS micelles and DPC/CHAPS doped with cholesterol sulfate micelles have been investigated. Chemical shift perturbations and line broadening analysis has been conducted, and the initial results suggest a KD of physiological importance. Cross -correlation rates and the extent of chemical shift perturbation between the DPC/CHAPS… Advisors/Committee Members: Van Doren, Steven (advisor).

Subjects/Keywords: matrix metalloproteinase; extracellular components; binding site

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APA (6^th Edition):

Byrne, T. S. (2012). Structural interactions sites of matrix metalloproteinase-12 with collagen triple helix, micelles, and a natural product from green tea. (Thesis). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/33129

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Byrne, Todd S. “Structural interactions sites of matrix metalloproteinase-12 with collagen triple helix, micelles, and a natural product from green tea.” 2012. Thesis, University of Missouri – Columbia. Accessed February 27, 2021. http://hdl.handle.net/10355/33129.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Byrne, Todd S. “Structural interactions sites of matrix metalloproteinase-12 with collagen triple helix, micelles, and a natural product from green tea.” 2012. Web. 27 Feb 2021.

Vancouver:

Byrne TS. Structural interactions sites of matrix metalloproteinase-12 with collagen triple helix, micelles, and a natural product from green tea. [Internet] [Thesis]. University of Missouri – Columbia; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10355/33129.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Byrne TS. Structural interactions sites of matrix metalloproteinase-12 with collagen triple helix, micelles, and a natural product from green tea. [Thesis]. University of Missouri – Columbia; 2012. Available from: http://hdl.handle.net/10355/33129

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Ehrt, Christiane. Protein binding site comparison: The impact of binding site similarity on hit identification in early drug discovery.

Degree: 2019, Technische Universität Dortmund

URL: http://dx.doi.org/10.17877/DE290R-20262

► The aim of the present study was the identification of novel hit compounds for the inhibition of trypanothione synthetase (TryS) from organisms of the genus… (more)

▼ The aim of the present study was the identification of novel hit compounds for the inhibition of trypanothione synthetase (TryS) from organisms of the genus Leishmania. They are the causative agents of the so-called neglected diseases. There is an urgent need for novel therapeutics for these diseases as the current treatment methods are not sufficiently reliable when compared to the medical management for diseases prevalent in developed high-income countries. The basic idea of this work was to set up a structure-based drug repurposing workflow based on similarities between the ATP binding sites of TryS from Leishmania major and protein kinases. The latter enzymes are well characterised, and this approach benefits from the huge knowledge of drug-like small molecule inhibitors of protein kinases. However, the establishment of such a workflow requires the reliable interplay of multiple software methods for in silico structure-based modelling. The chosen workflow includes the comparative modelling of the enzymes under investigation, MD simulation studies, an in-depth analysis of pocket properties, the comparison of binding sites of TryS and kinases, and a subsequent molecular docking of known inhibitors of protein kinases which are most similar to TryS with respect to the ATP binding site properties. The breakneck developments in the field of in silico hit identification led to the emergence of a myriad of available methods to meet similar targets. Current state-of-the-art methods evolved for often applied structure-based methods such as molecular docking or pharmacophore searches. Unfortunately, methods for the prediction, analysis, and comparison of binding sites are less frequently applied. This led to the parallel development of numerous methods which differ in multiple aspects. This diversity necessitates reliable comparison and benchmark analyses to elucidate the most suitable approaches for a pre-defined scientific question. In consequence, a main part of the present work is dedicated to the comprehensive evaluation of developed software for the prediction and comparison of binding sites. The analyses shed light on the major strengths and restrictions of the methods under investigation. The results ensure that only the most reliable methods are chosen for the problem under investigation. For binding site prediction methods, we can pinpoint a restricted set of exceptionally reliable methods. The case is different for binding site comparison tools. We must finally conclude that the establishment of a consensus approach might be the most appropriate way to identify binding site similarities. Besides the comparison of binding sites based on physicochemical and shape properties, an alternative approach was tested for its applicability for the presented project. Based on the observation that some less closely related proteins binding to similar scaffolds share a common arrangement of SSEs in the ligand binding sites, it was hypothesised that finding similar arrangements of SSEs in unrelated proteins might facilitate… Advisors/Committee Members: Rauh, Daniel (advisor), Kast, Stefan M. (referee).

Subjects/Keywords: Structure-based design; Binding site identification; Binding site comparison; Secondary structure elements; Medicinal chemistry; Trypanothione synthetase; 570; 540; Enzym; Inhibitor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ehrt, C. (2019). Protein binding site comparison: The impact of binding site similarity on hit identification in early drug discovery. (Doctoral Dissertation). Technische Universität Dortmund. Retrieved from http://dx.doi.org/10.17877/DE290R-20262

Chicago Manual of Style (16^th Edition):

Ehrt, Christiane. “Protein binding site comparison: The impact of binding site similarity on hit identification in early drug discovery.” 2019. Doctoral Dissertation, Technische Universität Dortmund. Accessed February 27, 2021. http://dx.doi.org/10.17877/DE290R-20262.

MLA Handbook (7^th Edition):

Ehrt, Christiane. “Protein binding site comparison: The impact of binding site similarity on hit identification in early drug discovery.” 2019. Web. 27 Feb 2021.

Vancouver:

Ehrt C. Protein binding site comparison: The impact of binding site similarity on hit identification in early drug discovery. [Internet] [Doctoral dissertation]. Technische Universität Dortmund; 2019. [cited 2021 Feb 27]. Available from: http://dx.doi.org/10.17877/DE290R-20262.

Council of Science Editors:

Ehrt C. Protein binding site comparison: The impact of binding site similarity on hit identification in early drug discovery. [Doctoral Dissertation]. Technische Universität Dortmund; 2019. Available from: http://dx.doi.org/10.17877/DE290R-20262

University of Hawaii – Manoa

4. To, Albert. Methylglyoxal-Modification of Human Serum Albumin Alters Bilirubin Binding.

Degree: 2017, University of Hawaii – Manoa

URL: http://hdl.handle.net/10125/51181

►

M.S. University of Hawaii at Manoa 2015.

The glycation of protein is a non-enzymatic post-translational modification targeting terminal amines of positively-charged amino acids, and has… (more)

Subjects/Keywords: Human serum albumin; methylglyoxal; glycation; bilirubin; arginine; structure; conformation; drug binding site I; drug binding site II

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APA (6^th Edition):

To, A. (2017). Methylglyoxal-Modification of Human Serum Albumin Alters Bilirubin Binding. (Thesis). University of Hawaii – Manoa. Retrieved from http://hdl.handle.net/10125/51181

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

To, Albert. “Methylglyoxal-Modification of Human Serum Albumin Alters Bilirubin Binding.” 2017. Thesis, University of Hawaii – Manoa. Accessed February 27, 2021. http://hdl.handle.net/10125/51181.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

To, Albert. “Methylglyoxal-Modification of Human Serum Albumin Alters Bilirubin Binding.” 2017. Web. 27 Feb 2021.

Vancouver:

To A. Methylglyoxal-Modification of Human Serum Albumin Alters Bilirubin Binding. [Internet] [Thesis]. University of Hawaii – Manoa; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10125/51181.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

To A. Methylglyoxal-Modification of Human Serum Albumin Alters Bilirubin Binding. [Thesis]. University of Hawaii – Manoa; 2017. Available from: http://hdl.handle.net/10125/51181

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Graña, Adolfo Orro. Examination of the role of binding site water molecules in molecular recognition.

Degree: 2012, SciLifeLab Stockholm

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200164

► A set of algorithms were designed, implemented and evaluated in order to, first, identifyclusters of conserved waters in binding pockets, i.e. hydration sites. Then,… (more)

Subjects/Keywords: Free energy of binding; enthalpy; entropy; ligand; hydration site; ligand-protein binding.

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APA (6^th Edition):

Graña, A. O. (2012). Examination of the role of binding site water molecules in molecular recognition. (Thesis). SciLifeLab Stockholm. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200164

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Graña, Adolfo Orro. “Examination of the role of binding site water molecules in molecular recognition.” 2012. Thesis, SciLifeLab Stockholm. Accessed February 27, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200164.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Graña, Adolfo Orro. “Examination of the role of binding site water molecules in molecular recognition.” 2012. Web. 27 Feb 2021.

Vancouver:

Graña AO. Examination of the role of binding site water molecules in molecular recognition. [Internet] [Thesis]. SciLifeLab Stockholm; 2012. [cited 2021 Feb 27]. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200164.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Graña AO. Examination of the role of binding site water molecules in molecular recognition. [Thesis]. SciLifeLab Stockholm; 2012. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200164

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

6. Leonar, Erica. Family A G protein-coupled receptor ligand interactions: the role of the extracellular region.

Degree: Medical Sciences, 2017, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/57418 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:43382/SOURCE02?view=true

► Increasing interest in the role of the extracellular loops (ECL) in family A G protein-coupled receptor (GPCR) function stems from (i) the discovery that many… (more)

▼ Increasing interest in the role of the extracellular loops (ECL) in family A G protein-coupled receptor (GPCR) function stems from (i) the discovery that many allosteric modulators of alpha branch receptors interact with the ECL, (ii) predictions that this region forms an initial interaction site for orthosteric ligands, (iii) ECL mutations alter receptor signalling and (iv) the ECL interacts with peptide ligands from the gamma branch receptors. This thesis investigated the role of the ECL and surrounding regions in allosteric and orthosteric ligand interactions across family A GPCRs using the alpha branch beta2 adrenoceptor (b2AR) and the gamma branch complement 5a receptor (C5aR).THRX100361 and tacrine displayed positive modulation of 3H-dihydroalprenolol (DHA) dissociation from the b2AR but negative modulation of b2AR activation. Using docking and mutagenesis, an allosteric site comprised of residues from ECL2 (F193) and the top of helices 6 (H296) and 7 (K305 and Y308) was identified. Mutation of these residues to alanine reduced the modulatory actions of THRX100361 and tacrine. These mutations also increased the dissociation rate of 3H-DHA. This supports the existence of a metastable binding site on the b2AR as predicted in computational studies and that this region is important in orthosteric and allosteric interactions.PMX53 is potent inhibitor of the C5aR and has previously been described as a non-competitive antagonist in myeloperoxidase and calcium release assays. Surprisingly, in this study, PMX53 behaved as a competitive antagonist of C5a-mediated Gi activation. This discrepancy suggests that PMX53 has a slow off rate, resulting in hemi-equilibrium conditions in signalling assays with short incubation times and is in fact a competitive antagonist. Supporting this, docking of PMX53 into a homology model suggested interactions with ECL1-2 and helices 2,3,5,6-7 including residues involved in C5a binding. The affinity of PMX53 is 400 fold lower at the mouse compared to human and rat C5aR. Docking and sequence alignment suggested that 2 residues in ECL2 may contribute to this difference. The human to mouse mutation L187V has no effect, while D191N increased PMX53 potency, indicating that ECL2 may play a role in PMX53 binding but does account for the species variation in affinity. Further studies are required to fully understand PMX53 molecular mechanism of action.The data in this thesis suggest an important role for the ECL2 in family A GPCRs. Advisors/Committee Members: Finch, Angela, Medical Sciences, Faculty of Medicine, UNSW, Griffith, Renate, Medical Sciences, Faculty of Medicine, UNSW, Woodruff, Trent, School of Biomedical Sciences, Faculty of Medicine, The University of Queensland.

Subjects/Keywords: vestibule; GPCR; allosteric modulator; extracellular binding site; ligand binding kinetics; extracellular loop

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Leonar, E. (2017). Family A G protein-coupled receptor ligand interactions: the role of the extracellular region. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/57418 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:43382/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Leonar, Erica. “Family A G protein-coupled receptor ligand interactions: the role of the extracellular region.” 2017. Doctoral Dissertation, University of New South Wales. Accessed February 27, 2021. http://handle.unsw.edu.au/1959.4/57418 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:43382/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Leonar, Erica. “Family A G protein-coupled receptor ligand interactions: the role of the extracellular region.” 2017. Web. 27 Feb 2021.

Vancouver:

Leonar E. Family A G protein-coupled receptor ligand interactions: the role of the extracellular region. [Internet] [Doctoral dissertation]. University of New South Wales; 2017. [cited 2021 Feb 27]. Available from: http://handle.unsw.edu.au/1959.4/57418 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:43382/SOURCE02?view=true.

Council of Science Editors:

Leonar E. Family A G protein-coupled receptor ligand interactions: the role of the extracellular region. [Doctoral Dissertation]. University of New South Wales; 2017. Available from: http://handle.unsw.edu.au/1959.4/57418 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:43382/SOURCE02?view=true

University of Alberta

7. Chen, Ke. In-silico characterization and prediction of protein-small ligand interactions.

Degree: PhD, Department of Electrical and Computer Engineering, 2011, University of Alberta

URL: https://era.library.ualberta.ca/files/cc08hg940

► Proteins, which participate in virtually every process within cells, implement many of their functions through interactions with various ligands. Although a substantial effort in characterization… (more)

▼ Proteins, which participate in virtually every process within cells, implement many of their functions through interactions with various ligands. Although a substantial effort in characterization and prediction of protein-ligand interactions was observed in the past two decades, these subjects remain far from completion. This dissertation focuses on computational (in-silico) analysis and prediction of the protein-small ligand interactions, with particular emphasis on the protein-nucleotide interactions. We start by analyzing regularities, referred to as the interaction patterns, in the atomic-level protein-small ligand interactions which lead to the discovery of ten interaction patterns that cover majority of the known interactions. The discovery of these interaction patterns demonstrates that protein-ligand interactions can be predicted for a given protein. Next, we performed an extensive comparative analysis of the predictive performance of ten representative methods that predict binding residues and binding sites for small organic ligands. Our results reveal that although the predictive quality of these methods was significantly improved during the past decade, there is still a large room for further improvements, particularly when predicting for certain types of the organic compounds. We also found a few limitations of the existing methods which motivate the development of new predictors of the protein-small organic ligand interactions. Consequently, we proposed two methods that address prediction of the protein-nucleotide interactions. We selected nucleotides from among the organic compounds because they are highly abundant and ubiquitous (they are involved in a wide range of biological processes), and thus they constitute an important and challenging problem. The first method predicts nucleotide binding residues from protein sequences, and the second method identifies the binding sites from protein structures. We empirically demonstrate that both, the sequence-based and the structure-based, methods significantly improve predictions over the existing state-of-the-art solutions. Our study aims to help with the characterization and annotation of biological functions of proteins and elucidation of the molecular-level mechanisms of cellular activities, and it provides tools that can be used to implement improved molecular-docking based rational drug discovery protocols.

Subjects/Keywords: interaction; ligand; protein function annotation; binding site; protein; prediction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, K. (2011). In-silico characterization and prediction of protein-small ligand interactions. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/cc08hg940

Chicago Manual of Style (16^th Edition):

Chen, Ke. “In-silico characterization and prediction of protein-small ligand interactions.” 2011. Doctoral Dissertation, University of Alberta. Accessed February 27, 2021. https://era.library.ualberta.ca/files/cc08hg940.

MLA Handbook (7^th Edition):

Chen, Ke. “In-silico characterization and prediction of protein-small ligand interactions.” 2011. Web. 27 Feb 2021.

Vancouver:

Chen K. In-silico characterization and prediction of protein-small ligand interactions. [Internet] [Doctoral dissertation]. University of Alberta; 2011. [cited 2021 Feb 27]. Available from: https://era.library.ualberta.ca/files/cc08hg940.

Council of Science Editors:

Chen K. In-silico characterization and prediction of protein-small ligand interactions. [Doctoral Dissertation]. University of Alberta; 2011. Available from: https://era.library.ualberta.ca/files/cc08hg940

University of Saskatchewan

8. Yan, Xiaoyu. Characterization of the Hoxa2 binding site in dual specificity tyrosine kinase 4 (Dyrk4) and high temperature requirement factor A 3 (HtrA3) genes.

Degree: 2008, University of Saskatchewan

URL: http://hdl.handle.net/10388/etd-04292008-135307

► Hox proteins are evolutionarily conserved transcription factors that control important developmental pathways in morphogenesis of the embryo. The Hoxa2 gene is expressed in the developing… (more)

▼ Hox proteins are evolutionarily conserved transcription factors that control important developmental pathways in morphogenesis of the embryo. The Hoxa2 gene is expressed in the developing central nervous system in rhombomeres 2 to 7 and affects cellular differentiation. Few target genes of Hoxa2 protein have been identified so far and its mechanisms of regulating gene expression remain elusive. Previous work in our laboratory isolated Hoxa2 protein binding sequences from the E18 mouse spinal cord and hindbrain tissues using chromatin immunoprecipitation (ChIP). All isolated DNA fragments contain conserved GATG motifs. Sequence analysis revealed that one fragment belongs to the high temperature requirement factor A 3 (HtrA3) gene and another fragment belongs to the Dual specificity tyrosine kinase 4 (Dyrk4) gene. In this study, direct binding of Hoxa2 protein to the HtrA3 and Dyrk4 fragments was confirmed by electrophoretic mobility shift assays (EMSA). Site-directed mutagenesis and EMSA studies revealed that Hoxa2 protein binds to the multiple GATG motifs within these fragments. HtrA3 fragment also repressed luciferase gene expression in transient transfection and luciferase assays. Mutation of the DNA fragment showed that the repressive activity was affected by the GATG motifs, suggesting Hoxa2 protein regulated gene expression by binding to the GATG motif in the cis-regulatory element. In contrast to the inhibitory activity of Hoxa2 protein, a Hoxa2-VP16 fusion protein (Hoxa2 fused with an activation domain of a virion protein from herpes simplex virus) transactivates the luciferase expression by binding to GATG sites. RT-PCR and immunohistochemistry analysis revealed an upregulation of HtrA3 expression in Hoxa2-/- mice. This observation correlates with the inhibitory role of Hoxa2 protein acting upon the HtrA3 fragment in luciferase assays. Our data suggest that HtrA3 is a direct in vivo downstream target of Hoxa2 protein and support the activity regulation model in which Hox proteins selectively regulate target genes through occupation of multiple monomer binding sites. Advisors/Committee Members: Nazarali, Adil J., Yang, Jian, Xiao, Wei, Mousseau, Darrell D., Alcorn, Jane.

Subjects/Keywords: Hoxa2 binding site; Dyrk4; HtrA3

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APA (6^th Edition):

Yan, X. (2008). Characterization of the Hoxa2 binding site in dual specificity tyrosine kinase 4 (Dyrk4) and high temperature requirement factor A 3 (HtrA3) genes. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/etd-04292008-135307

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yan, Xiaoyu. “Characterization of the Hoxa2 binding site in dual specificity tyrosine kinase 4 (Dyrk4) and high temperature requirement factor A 3 (HtrA3) genes.” 2008. Thesis, University of Saskatchewan. Accessed February 27, 2021. http://hdl.handle.net/10388/etd-04292008-135307.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yan, Xiaoyu. “Characterization of the Hoxa2 binding site in dual specificity tyrosine kinase 4 (Dyrk4) and high temperature requirement factor A 3 (HtrA3) genes.” 2008. Web. 27 Feb 2021.

Vancouver:

Yan X. Characterization of the Hoxa2 binding site in dual specificity tyrosine kinase 4 (Dyrk4) and high temperature requirement factor A 3 (HtrA3) genes. [Internet] [Thesis]. University of Saskatchewan; 2008. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10388/etd-04292008-135307.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yan X. Characterization of the Hoxa2 binding site in dual specificity tyrosine kinase 4 (Dyrk4) and high temperature requirement factor A 3 (HtrA3) genes. [Thesis]. University of Saskatchewan; 2008. Available from: http://hdl.handle.net/10388/etd-04292008-135307

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Wayne State University

9. Alger, Tara Shane. Influence Of Mechanical Cues And The Extracellular Matrix On Cell Migration Patterns And The Proliferation Rates Of Cells.

Degree: MS, Biological Sciences, 2013, Wayne State University

URL: https://digitalcommons.wayne.edu/oa_theses/225

► The mechanical environment of a cell and its tissue can impact multiple biological processes including development, wound healing, and metastasis. Specific cellular behaviors influenced… (more)

▼ The mechanical environment of a cell and its tissue can impact multiple biological processes including development, wound healing, and metastasis. Specific cellular behaviors influenced by the mechanical microenvironment include differentiation, morphology, apoptosis, migration, and proliferation. In this thesis I have focused specifically on the effect of environmental stiffness and applied mechanical forces on cellular migration and proliferation, respectively. Using two different applications, both tailored to evaluate the mechanical forces alone on cellular behavior, I attempted to simulate the mechanical composition of the in vivo tissue microenvironments in vitro using polyacrylamide hydrogels. To test whether cells maintain a mechanical memory for a specific stiffness in vitro, we utilized a substrate that differentially polymerizes with variant levels of UV exposure and analyzed the directional migration patterns upon different rigidities. These substrates did not show any particular directional preference for migration, however cells did seem to be able to sense variation in stiffness based on the results of a morphology assay. It is unknown whether the cells were unable to sense differences in neighboring stiffnesses due to the extracellular matrix or to the hydrogel itself. To examine the proliferation rates of cells given an applied mechanical stimulus, we created hydrogels embedded with magnetic microbeads that provided a tugging and pulling motion mimicking the effects of adherent cells on their neighboring environment. The observed increase in proliferation upon mechanical stimulation was dependent on the presence of fibronectin coated to the hydrogel surface, indicating that this protein is essential for the mechanosensing response of cells. I hypothesized that compacted conformations of fibronectin are released during mechanical stimulation, opening cryptic binding sites for cells to adhere to. I tested the presence of these cryptic binding sites by chemically crosslinking the ECM prior to stimulation, as well as adding the competitive peptide arginine-glycine-aspartic acid (RGD). Both of these resulted in the decrease in proliferation rate during stimulation but had no effect in control cells. The surface receptor protein responsible for activating these cascades is still unknown. After testing the activity level of â1 integrin, a known mechanosensor and binding partner to fibronectin, there was no difference in the activity of this particular integrin subunit, strongly suggesting this is not the integrin activated by our mechanical stimulus. Protein activity studies found that the phosphorylation state of both Focal Adhesion Kinase (FAK), as well as, Extracellular Signal-Regulated Kinase (ERK) are increased upon stimulation, indicating that these two signaling cascades lead to the increase in the cell cycle activity. Further studies are required to determine the link between the fibronectin cryptic sites and the downstream signaling cascades activated during stimulation. Both of these cell… Advisors/Committee Members: Karen A. Beningo.

Subjects/Keywords: cryptic binding site; fibronectin; integrin; mechanotransduction; proliferation; Cell Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alger, T. S. (2013). Influence Of Mechanical Cues And The Extracellular Matrix On Cell Migration Patterns And The Proliferation Rates Of Cells. (Masters Thesis). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_theses/225

Chicago Manual of Style (16^th Edition):

Alger, Tara Shane. “Influence Of Mechanical Cues And The Extracellular Matrix On Cell Migration Patterns And The Proliferation Rates Of Cells.” 2013. Masters Thesis, Wayne State University. Accessed February 27, 2021. https://digitalcommons.wayne.edu/oa_theses/225.

MLA Handbook (7^th Edition):

Alger, Tara Shane. “Influence Of Mechanical Cues And The Extracellular Matrix On Cell Migration Patterns And The Proliferation Rates Of Cells.” 2013. Web. 27 Feb 2021.

Vancouver:

Alger TS. Influence Of Mechanical Cues And The Extracellular Matrix On Cell Migration Patterns And The Proliferation Rates Of Cells. [Internet] [Masters thesis]. Wayne State University; 2013. [cited 2021 Feb 27]. Available from: https://digitalcommons.wayne.edu/oa_theses/225.

Council of Science Editors:

Alger TS. Influence Of Mechanical Cues And The Extracellular Matrix On Cell Migration Patterns And The Proliferation Rates Of Cells. [Masters Thesis]. Wayne State University; 2013. Available from: https://digitalcommons.wayne.edu/oa_theses/225

Univerzitet u Beogradu

10. Milić, Marija M., 1982-. Uticaj supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABAA receptora na ponašanje pacova u Morisovom vodenom lavirintu.

Degree: Farmaceutski fakultet, 2014, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:8539/bdef:Content/get

►

Farmacija - Farmakologija / Pharmacy - Pharmacology

Klasični benzodiazepini deluju kao neselektivni pozitivni modulatori GABAA receptora koji sadrže α1, α2, α3 i α5 podjedinicu, i… (more)

▼

Farmacija - Farmakologija / Pharmacy - Pharmacology

Klasični benzodiazepini deluju kao neselektivni pozitivni modulatori GABAA receptora koji sadrže α1, α2, α3 i α5 podjedinicu, i u uslovima kliničke primene dovode do razvoja anterogradne amnezije. Nasuprot tome, negativna modulacija na nivou ovih receptora dovodi se u vezu sa poboljšanjem odreñenih tipova memorije kod ljudi i životinja. Uprkos brojnim istraživanjima, precizna uloga različitih podjedinica GABAA receptora u memorijskim efektima benzodiazepina nije u potpunosti rasvetljena. Tome doprinosi činjenica da uticaj diazepama u memorijskim testovima kod knock in i knock out miševa nije ispitan u potpunosti, ali i nedostatak selektivnih liganada i odgovarajućih farmakoloških istraživanja. Ekvivalent pamćenju kod ljudi jeste specifičan oblik promene ponašanja eksperimentalnih životinja koji se kroz brojne parametre može kvalitativno i kvantitativno opisivati. Morisov vodeni lavirint (MVL) je jedan od najčešće korišćenih laboratorijskih testova u bihejvioralnim neuronaukama uopšte, a primenjuje se za proučavanje neurobiologije i neurofarmakologije prostornog učenja i memorije kod oglednih pacova. U okviru ove disertacije, primenom Morisovog vodenog lavirinta ispitan je uticaj supstanci koje deluju preko benzodiazepinskog mesta vezivanja GABAA receptora na učenje i pamćenje kod pacova Wistar soja. Cilj je bio da se uz pomoć supstanci koje imaju različite kombinacije afiniteta i efikasnosti na ovim veznim mestima utvrdi relativni doprinos svake od podjedinica GABAA receptora u memorijskim efektima koji se zapažaju u korišćenom testu, kao i stadijum memorijskog procesa (akvizicija, konsolidacija ili pozivanje memorije) koji je podložan uticaju pozitivnih neselektivnih modulatora. U istraživanju je pokazano da neselektivni pozitivni modulatori (diazepam i midazolam) na dozno-zavisan način dovode do oštećenja učenja i pamćenja u MVL-u. S obzirom na doze koje su pokazale aktivnost, ne može se isključiti i doprinos nekih nekognitivnih efekata u ukupnoj inkapacitaciji životinja koja se vidi u MVL-u. Efekti benzodiazepina u MVL-u uglavnom su ograničeni na fazu akvizicije memorije, s time što je pokazano da midazolam može da dovede i do oštećenja pozivanja...

Advisors/Committee Members: Savić, Miroslav, 1973-.

Subjects/Keywords: GABAА receptors; benzodiazepine binding site; anterograde amnesia; Morris water maze

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Milić, Marija M., 1. (2014). Uticaj supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABAA receptora na ponašanje pacova u Morisovom vodenom lavirintu. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:8539/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Milić, Marija M., 1982-. “Uticaj supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABAA receptora na ponašanje pacova u Morisovom vodenom lavirintu.” 2014. Thesis, Univerzitet u Beogradu. Accessed February 27, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:8539/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Milić, Marija M., 1982-. “Uticaj supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABAA receptora na ponašanje pacova u Morisovom vodenom lavirintu.” 2014. Web. 27 Feb 2021.

Vancouver:

Milić, Marija M. 1. Uticaj supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABAA receptora na ponašanje pacova u Morisovom vodenom lavirintu. [Internet] [Thesis]. Univerzitet u Beogradu; 2014. [cited 2021 Feb 27]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:8539/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Milić, Marija M. 1. Uticaj supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABAA receptora na ponašanje pacova u Morisovom vodenom lavirintu. [Thesis]. Univerzitet u Beogradu; 2014. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:8539/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Francisco

11. Spitzer, Russell Alexander. Applications of a Surface-Based Protein Binding Site Comparison Methodology.

Degree: Biological and Medical Informatics, 2013, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/1qb3n47d

► Protein similarity has been used for the annotation and classification of proteins when the structure of the protein is available. Protein similarity comparisons may be… (more)

▼ Protein similarity has been used for the annotation and classification of proteins when the structure of the protein is available. Protein similarity comparisons may be made on a local or global basis and may consider sequence information and differing levels of structural information. This dissertation details the method Surflex PSIM, a local 3D method that compares the surfaces of protein binding sites. PSIM is a local 3D method that compares protein binding site surfaces in full atomic detail. The approach is based on the morphological similarity method (Surflex-Sim) which has been widely applied for global comparison of small molecules. This methodology has the ability to determine the differences between very similar proteins with different ligand binding specificity and the ability to correctly align extremely divergent proteins with only a small region of similarity. PSIM performed well on known standards for binding site comparisons. In a docking benchmark study, PSIM was used to assist in multi-structure docking protocols. In these protocols, proper selection of target structures can reduce time required for screening and increase accuracy. Selection of a minimal representative set of docking target conformations was performed automatically using PSIM. Several docking targets, for which unsatisfactory results had been obtained used a single-structure protocol, yielded substantial improvements using the PSIM-aided multi-structure docking protocol. Further development of an automated binding-site detection algorithm allowed for PSIM to be used as screening tool for annotating proteins with unknown function. A dataset was created of proteins whose function was determined after their crystallization. PSIM was able to automatically detect binding sites on a majority of these proteins and successfully match them to proteins that were present in the PDB at the time of crystallization that have the same function. PSIM was further used to explore possible functions for several proteins whose function is still unknown. The main contribution of this dissertation is a fast and accurate method for the comparison of protein binding sites agnostic of sequence information. This methodology has applications in the analysis of ligand specificity analysis and the annotation of proteins with unknown function.

Subjects/Keywords: Bioinformatics; Biophysics; Binding-Site Similarity; Functional Annotation; Protein

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Spitzer, R. A. (2013). Applications of a Surface-Based Protein Binding Site Comparison Methodology. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/1qb3n47d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Spitzer, Russell Alexander. “Applications of a Surface-Based Protein Binding Site Comparison Methodology.” 2013. Thesis, University of California – San Francisco. Accessed February 27, 2021. http://www.escholarship.org/uc/item/1qb3n47d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Spitzer, Russell Alexander. “Applications of a Surface-Based Protein Binding Site Comparison Methodology.” 2013. Web. 27 Feb 2021.

Vancouver:

Spitzer RA. Applications of a Surface-Based Protein Binding Site Comparison Methodology. [Internet] [Thesis]. University of California – San Francisco; 2013. [cited 2021 Feb 27]. Available from: http://www.escholarship.org/uc/item/1qb3n47d.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Spitzer RA. Applications of a Surface-Based Protein Binding Site Comparison Methodology. [Thesis]. University of California – San Francisco; 2013. Available from: http://www.escholarship.org/uc/item/1qb3n47d

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Brandeis University

12. Yao, Tianjiong. Identification of the binding site for ammonia in GMP reductase.

Degree: 2015, Brandeis University

URL: http://hdl.handle.net/10192/29093

► The overall reaction of guanosine monophosphate reductase (GMPR) converts GMP to IMP by using NADPH as a cofactor and it includes two sub-steps: (1) a… (more)

Subjects/Keywords: GMP reductase; ammonia binding site; steady state; pre-steady state

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APA (6^th Edition):

Yao, T. (2015). Identification of the binding site for ammonia in GMP reductase. (Thesis). Brandeis University. Retrieved from http://hdl.handle.net/10192/29093

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yao, Tianjiong. “Identification of the binding site for ammonia in GMP reductase.” 2015. Thesis, Brandeis University. Accessed February 27, 2021. http://hdl.handle.net/10192/29093.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yao, Tianjiong. “Identification of the binding site for ammonia in GMP reductase.” 2015. Web. 27 Feb 2021.

Vancouver:

Yao T. Identification of the binding site for ammonia in GMP reductase. [Internet] [Thesis]. Brandeis University; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10192/29093.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yao T. Identification of the binding site for ammonia in GMP reductase. [Thesis]. Brandeis University; 2015. Available from: http://hdl.handle.net/10192/29093

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia State University

13. Lamichhane, Hari Prasad. Calculated Vibrational Properties of Quinones in Photosynthetic Reaction Centers.

Degree: PhD, Physics and Astronomy, 2011, Georgia State University

URL: https://scholarworks.gsu.edu/phy_astr_diss/51

► This dissertation presents a detailed computational investigation into the vibrational properties of quinones involved in solar energy conversion processes in photosynthetic reaction centers. In… (more)

▼ This dissertation presents a detailed computational investigation into the vibrational properties of quinones involved in solar energy conversion processes in photosynthetic reaction centers. In particular, we focus on the vibrational properties of the ubiquinone molecule that occupies the Q_A binding site in purple bacterial photosynthetic reaction centers. To provide a foundation upon which to base computational studies of pigments in protein binding sites density functional theory based calculations of the vibrational properties of neutral ubiquinone in the gas phase and in solvent were undertaken. From single point energy calculations it was shown that at least eight ubiquinone conformers, each with slightly different FTIR spectra, could be present in solvent at room temperature. The calculated and experimental spectra for neutral ubiquinone in solution are very different from the spectra associated with ubiquinone in the Q_A binding in purple bacterial reaction centers. For this reason an ONIOM method was undertaken in which the pigment was treated using density functional theory based methods while the protein was treated using molecular mechanics. The ONIOM calculations not only modeled the experimental Q_A FTIR difference spectra but also resolved the long standing issue of whether a very strong hydrogen bond exists between the bound ubiquinone and the imidazole nitrogen of a histidine residue (HisM219). To further validate the usefulness of the ONIOM approach experimental isotope edited FTIR spectra obtained using purple bacterial reaction centers with a range of chainless symmetrical quinones incorporated were modeled. Again, the agreement between the calculated and experimental spectra is outstanding. We also modeled the vibrational properties of the ubisemiquinone anion radical both in solvent and in the Q_A binding site. Vibrational modes of ubisemiquinone display a greater degree of mixing of the various molecular groups of the molecule. Nonetheless the calculated FTIR spectra for ubisemiquinone in solution and in the Q_A site agree very well with that found experimentally. Vibrational frequencies of ubisemiquinone obtained from ONIOM calculated Raman spectra also agree very well with that found in experimental resonance Raman spectra associated with the ubisemiquinone anion radical in the Q_A binding site. Advisors/Committee Members: Dr. Gary Hastings.

Subjects/Keywords: Ubiquinone; Vibrational frequency; QA binding site; ONIOM method; Photosynthesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lamichhane, H. P. (2011). Calculated Vibrational Properties of Quinones in Photosynthetic Reaction Centers. (Doctoral Dissertation). Georgia State University. Retrieved from https://scholarworks.gsu.edu/phy_astr_diss/51

Chicago Manual of Style (16^th Edition):

Lamichhane, Hari Prasad. “Calculated Vibrational Properties of Quinones in Photosynthetic Reaction Centers.” 2011. Doctoral Dissertation, Georgia State University. Accessed February 27, 2021. https://scholarworks.gsu.edu/phy_astr_diss/51.

MLA Handbook (7^th Edition):

Lamichhane, Hari Prasad. “Calculated Vibrational Properties of Quinones in Photosynthetic Reaction Centers.” 2011. Web. 27 Feb 2021.

Vancouver:

Lamichhane HP. Calculated Vibrational Properties of Quinones in Photosynthetic Reaction Centers. [Internet] [Doctoral dissertation]. Georgia State University; 2011. [cited 2021 Feb 27]. Available from: https://scholarworks.gsu.edu/phy_astr_diss/51.

Council of Science Editors:

Lamichhane HP. Calculated Vibrational Properties of Quinones in Photosynthetic Reaction Centers. [Doctoral Dissertation]. Georgia State University; 2011. Available from: https://scholarworks.gsu.edu/phy_astr_diss/51

Université Paris-Sud – Paris XI

14. Roudaut, Hermine. Découverte et caractérisation pharmacologique de nouveaux antagonistes du récepteur smoothened : les composés mrt : Discovery and pharmacological characterization of novel potent smoothened antagonists : the mrt compounds.

Degree: Docteur es, Neurosciences, 2011, Université Paris-Sud – Paris XI

URL: http://www.theses.fr/2011PA11T073

► La voie de signalisation Sonic Hedgehog (Shh) joue un rôle fondamental au cours de l’embryogenèse pour la mise en place de nombreux tissus. Elle persiste… (more)

▼ La voie de signalisation Sonic Hedgehog (Shh) joue un rôle fondamental au cours de l’embryogenèse pour la mise en place de nombreux tissus. Elle persiste à l’âge adulte et régulerait notamment le contrôle de fonctions cérébrales. Son activation requiert la liaison d’un peptide Shh sur le récepteur Patched (Ptc) qui réprime l’activité constitutive de Smoothened (Smo), un récepteur apparenté à la famille des récepteurs couplés aux protéines G (RCPG). Récemment, des essais cliniques pour le traitement de médulloblastomes et de diverses tumeurs solides chez l’Homme ont été menés avec des antagonistes de Smo. Cependant, ces molécules ont révélé des limitations à leur utilisation puisque des résistances au traitement sont apparues. Le travail de cette thèse a conduit au développement d’un modèle pharmacophorique des antagonistes de Smo qui a ensuite permis le criblage virtuel d’une banque de molécules et l’identification de nouvelles familles d’antagonistes de Smo. L’acylthiourée MRT-10 et l’acylurée MRT-14 ont été les deux premiers composés caractérisés. Des études de relations structure-activité ont permis l’identification d’une nouvelle famille d’inhibiteurs du récepteur Smo de haute affinité à laquelle l’acylguanidine MRT-83 appartient. Ce composé s’adapte parfaitement au modèle pharmacophorique des antagonistes de Smo. Les modifications structurales que MRT-83 présentes en comparaison avec les deux têtes de séries précédemment caractérisées sont à l’origine du gain d’activité de MRT-83 sur de nombreux tests cellulaires mettant en jeu l’activation de la voie Shh. Le composé MRT-83 inhibe la liaison de la BODIPY-cyclopamine sur le récepteur Smo humain et bloque la prolifération des précurseurs des cellules granulaires de rat avec une affinité de l’ordre du nanomolaire, comparable à celle des antagonistes de référence de Smo tels que le GDC-0449 et le LDE-225. Malgré l’homologie de séquence entre Smo et la famille des récepteurs Frizzled impliqués dans la signalisation Wnt, le composé MRT-83 ne présente aucun effet sur la voie Wnt. MRT-83 bloque la translocation de Smo dans le cil primaire induite par l’activation de la voie Shh dans les cellules NT2, une lignée issue d’un tératocarcinome humain, contrairement à l’antagoniste de Smo de référence, la cyclopamine qui induit l’adressage du récepteur dans le cil primaire. L’injection stéréotaxique dans le ventricule latéral de cerveau de souris adulte de MRT-83, contrairement à celle d’un composé de structure analogue, dépourvu d’activité sur Smo, inhibe l’expression des transcrits de Ptc induite par l’injection de Shh dans la zone sous-ventriculaire, l’une des deux principales aires de neurogenèse adulte. Ces résultats démontrent que les dérivés MRT bloquent également la signalisation Shh in vivo. Ainsi, les composés MRT-10, MRT-14, MRT-83 et les molécules de structure analogues caractérisées sont de puissants antagonistes de Smo. Ces molécules constituent de nouveaux outils pharmacologiques qui pourraient permettre d’améliorer notre compréhension des mécanismes… Advisors/Committee Members: Ruat, Martial (thesis director).

Subjects/Keywords: Smoothened; Antagoniste; Modèle pharmacophorique; Site de liaison; Cil primaire; Smoothened; Antagonist; Pharmacophoric model; Binding site; Primary cilium

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roudaut, H. (2011). Découverte et caractérisation pharmacologique de nouveaux antagonistes du récepteur smoothened : les composés mrt : Discovery and pharmacological characterization of novel potent smoothened antagonists : the mrt compounds. (Doctoral Dissertation). Université Paris-Sud – Paris XI. Retrieved from http://www.theses.fr/2011PA11T073

Chicago Manual of Style (16^th Edition):

Roudaut, Hermine. “Découverte et caractérisation pharmacologique de nouveaux antagonistes du récepteur smoothened : les composés mrt : Discovery and pharmacological characterization of novel potent smoothened antagonists : the mrt compounds.” 2011. Doctoral Dissertation, Université Paris-Sud – Paris XI. Accessed February 27, 2021. http://www.theses.fr/2011PA11T073.

MLA Handbook (7^th Edition):

Roudaut, Hermine. “Découverte et caractérisation pharmacologique de nouveaux antagonistes du récepteur smoothened : les composés mrt : Discovery and pharmacological characterization of novel potent smoothened antagonists : the mrt compounds.” 2011. Web. 27 Feb 2021.

Vancouver:

Roudaut H. Découverte et caractérisation pharmacologique de nouveaux antagonistes du récepteur smoothened : les composés mrt : Discovery and pharmacological characterization of novel potent smoothened antagonists : the mrt compounds. [Internet] [Doctoral dissertation]. Université Paris-Sud – Paris XI; 2011. [cited 2021 Feb 27]. Available from: http://www.theses.fr/2011PA11T073.

Council of Science Editors:

Roudaut H. Découverte et caractérisation pharmacologique de nouveaux antagonistes du récepteur smoothened : les composés mrt : Discovery and pharmacological characterization of novel potent smoothened antagonists : the mrt compounds. [Doctoral Dissertation]. Université Paris-Sud – Paris XI; 2011. Available from: http://www.theses.fr/2011PA11T073

University of the Western Cape

15. Mwangi, Sarah Wambui. In silico investigation of glossina morsitans promoters .

Degree: 2013, University of the Western Cape

URL: http://hdl.handle.net/11394/3990

► Tsetse flies (Glossina spp) are the biological vectors for Trypanosomes, the causative magents of Human African Trypanosomiasis (HAT). HAT is a debilitating disease that continues… (more)

▼ Tsetse flies (Glossina spp) are the biological vectors for Trypanosomes, the causative magents of Human African Trypanosomiasis (HAT). HAT is a debilitating disease that continues to present a major public health problem and a key factor limiting rural development in vast regions of tropical Africa. To augment vector control efforts, the International Glossina Genome Initiative (IGGI) was established in 2004 with the ultimate goal of generating a fully annotated whole genome sequence for Glossina morsitans. A working draft genome of Glossina morsitans was availed in 2011. In this thesis, transcriptional regulatory features in Glossina morsitans were analysed using the draft genome. A method for TSS identification in the newly sequenced Glossina morsitans genome was developed using TSS-seq tags sampled from two developmental stages of Glossina morsitans. High throughput next generation sequencing reads obtained from Glossina morsitans larvae and pupae were used to locate transcription start sites (TSS) in the Glossina morsitans genome. TSS-seq tag clusters, defined as a minimum number of reads at the 5’ predicted UTR or first coding exon, were used to define transcription start sites. A total of 3134 tag clusters were identified on the Glossina genome. Approximately 45.4% (1424) of the tag clusters mapped to the first coding exons or their proximal predicted 5’UTR regions and include 31 tag clusters that mapped to transposons. A total of 1101 (35.1%) tag clusters mapped outside the genic region and/or scaffolds without gene predictions and may correspond to previously un-annotated transcripts or noncoding RNA TSS. The core promoter regions were classified as narrow or broad based on the number of TSS positions within a TSS-seq cluster. Majority (95%) of the core promoters analysed in this study were of the broad type while only 5% were of the narrow type. Comparison of canonical core promoter motif occurences between random and bona fide core promoters showed that, generally, the number of motifs in biologically functional genomic windows in the true dataset exceeded those in the random dataset (p <= 0.00164, 0.00135, 0.00185 for the narrow, broad with peak and broad without peak categories respectively). Frequency of motif co-occurrence in core promoter was found to be fundamentally different across various initiation patterns. Narrow core promoters recorded higher frequency of the TATA-box and INR motifs and two-way motif co-occurrence showed that the TATA-box-INR pair is over-represented in the narrow category. Broad core promoters showed higher frequency of the BREd and MTE motifs and two-way motif co-occurrence showed that the MTE-DPE pair is over-represented in broad core promoters. TATA-less promoters account for 77% of the core promoters in this analysis. TATA-less core promoters showed a higher frequency of the MTE and INR motifs in contrast to observations in Drosophila where the DPE motif has been reported to occur frequently in TATA-less promoters. These motif combinations suggest their equal… Advisors/Committee Members: Christoffels, Alan (advisor).

Subjects/Keywords: Glossina morsitans; Human African trypanosomiasis; Genome; TSS-seq; Transcription; Transcription start site; Promoter; Transcription regulation; Transcription factor binding site; Database

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APA (6^th Edition):

Mwangi, S. W. (2013). In silico investigation of glossina morsitans promoters . (Thesis). University of the Western Cape. Retrieved from http://hdl.handle.net/11394/3990

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mwangi, Sarah Wambui. “In silico investigation of glossina morsitans promoters .” 2013. Thesis, University of the Western Cape. Accessed February 27, 2021. http://hdl.handle.net/11394/3990.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mwangi, Sarah Wambui. “In silico investigation of glossina morsitans promoters .” 2013. Web. 27 Feb 2021.

Vancouver:

Mwangi SW. In silico investigation of glossina morsitans promoters . [Internet] [Thesis]. University of the Western Cape; 2013. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11394/3990.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mwangi SW. In silico investigation of glossina morsitans promoters . [Thesis]. University of the Western Cape; 2013. Available from: http://hdl.handle.net/11394/3990

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

16. Lyubetskaya, Anna. Transcription factor binding distribution and properties in prokaryotes.

Degree: PhD, Bioinformatics, 2015, Boston University

URL: http://hdl.handle.net/2144/15425

► The canonical model of transcriptional regulation in prokaryotes restricted binding site locations to promoter regions and suggested that the binding sequences serve as the main… (more)

▼ The canonical model of transcriptional regulation in prokaryotes restricted binding site locations to promoter regions and suggested that the binding sequences serve as the main determinants of binding. In this dissertation, I challenge these assumptions. As a member of the TB Systems Biology Consortium, I analyzed and validated ChIP-Seq and microarray experiments for over 100 transcription factors (TFs). In order to study the transcriptional functions of predicted binding sites, I integrated binding and expression data and assigned potential regulatory roles to 20% of the binding sites. Stronger binding sites were more often associated with regulation than weaker sites, suggesting a correlation between binding strength and regulatory impact. Seventy-six percent of the sites fell into annotated coding regions and a significant proportion was assigned to regulatory functions. To study the importance of binding sequences, I compared experimental sites with computational motif predictions. Although a conservative binding motif was found for most TFs, only a fraction of the observed motifs appeared bound in the experiment. Some low-affinity binding sites appeared occupied by the corresponding TF while many high-affinity binding sites were not. Interestingly, I found exactly the same nucleotide sequences (up to 15 residues long) bound in one area of the genome but not bound in another area, pointing to DNA accessibility as an important factor for in vivo binding. To investigate the evolutionary conservation of binding-site occupancy, sequence, and transcriptional impact, I analyzed ChIP-Seq and expression experiments for five conserved TFs for two-to-four Mycobacterial relatives. The regulon composition showed significantly less conservation than expected from the overall gene conservation level across Mycobacteria. Despite expectations, sequence conservation did not serve as a good indicator of whether or not a computationally predicted motif was bound experimentally; and in some cases, a fully conserved motif was bound in one relative but not in the other. Conservation of genic binding sites was higher than expected from the random model, adding to the evidence that at least some genic sites are functional. Understanding the evolutionary story of binding sites allowed me to explain unusual site configurations, some of which indicated a role for DNA looping.

Subjects/Keywords: Bioinformatics; ChIP-seq; Binding site; Prokaryotes; Regulon evolution; Transcriptional regulation; Transcription factor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lyubetskaya, A. (2015). Transcription factor binding distribution and properties in prokaryotes. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/15425

Chicago Manual of Style (16^th Edition):

Lyubetskaya, Anna. “Transcription factor binding distribution and properties in prokaryotes.” 2015. Doctoral Dissertation, Boston University. Accessed February 27, 2021. http://hdl.handle.net/2144/15425.

MLA Handbook (7^th Edition):

Lyubetskaya, Anna. “Transcription factor binding distribution and properties in prokaryotes.” 2015. Web. 27 Feb 2021.

Vancouver:

Lyubetskaya A. Transcription factor binding distribution and properties in prokaryotes. [Internet] [Doctoral dissertation]. Boston University; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/2144/15425.

Council of Science Editors:

Lyubetskaya A. Transcription factor binding distribution and properties in prokaryotes. [Doctoral Dissertation]. Boston University; 2015. Available from: http://hdl.handle.net/2144/15425

17. André, Éric. Étude de l’influence de modifications structurales sur la neuroglobine humaine : Study of the influence of structural modifications on the human neuroglobin.

Degree: Docteur es, Chimie, 2017, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2017SACLS145

►

La neuroglobine humaine (Ngb) est une globine découverte en 2000 dont la fonction principale demeure encore inconnue. Par comparaison avec l’hémoglobine (Hb) et la myoglobine… (more)

▼

La neuroglobine humaine (Ngb) est une globine découverte en 2000 dont la fonction principale demeure encore inconnue. Par comparaison avec l’hémoglobine (Hb) et la myoglobine (Mb), les globines les plus étudiées, la Ngb possède une séquence en acides aminés particulière. Il en résulte des caractéristiques structurales propres à la Ngb. L’hème, qui constitue le site actif de la Ngb, est hexacoordiné par l’histidine distale 64 et existe sous deux formes isomères A et B. La Ngb comprend également un pont disulfure Cys46-Cys55 intramoléculaire.La relation entre ces spécificités et d’éventuelles fonctions de la Ngb demeure cependant assez mal explorée. Notre objectif durant la thèse, était de mettre en évidence in vitro l’influence de différents éléments structuraux sur les propriétés et la réactivité de la Ngb. Pour ce faire, les mutations H64V, F106L, A90P et C46G ont été réalisées. Des études expérimentales à l’aide de spectrophotométrie UV-visible, de dichroisme circulaire et de RMN, ont été effectuées pour caractériser les mutants synthétisés, tester leur stabilité en fonction du pH et évaluer leur réactivité vis-à-vis de la fixation du ligand CN.Nous avons ainsi montré que la structure de la Ngb était influencée par la présence de l’histidine distale, du pont disulfure et de l’environnement de l’hème. L’étude, pour la première fois, des coefficients d’extinction molaire des protéines mutées a permis de souligner l’impact des acides aminés au voisinage de l’hème mais aussi du pont disulfure sur l’environnement électronique de l’hème. Nous avons aussi mis en évidence que le pont disulfure et les acides aminés mutés influaient sur la capacité de la forme isomère A de la Ngb à fixer le cyanure. La forme isomère B est en revanche peu impactée par ces deux paramètres. Cela soulève la question de l’existence et de la fonction des deux formes isomères de l’hème in vivo.

The physiological function of Human Neuroglobin (Ngb), discovered in 2000, is still unknown. Compared to other classical globins Haemoglobin and Myoglobin, Ngb has some structural specificities. Its haem, which is its reactive centre, is hexacoordinated by distal histidine 64 and exists under two isomer forms A and B. Moreover, Ngb possesses an intramolecular disulfide bridge between two cysteines 46 and 55.The relationship between its structural characteristics and its functions in vivo does not remain well-understood. The goal of this thesis was to underline the impact of some structural features on the Ngb properties and reactivity in vitro. Thus Ngb variants H64V, F106L, A90P and C46G were produced. Experimental studies were performed by UV-Visible spectrophotometry, circular dichroism and NMR. Variants were characterized : their stability as a function of pH were tested and their reactivity trough the CN binding reaction were evaluated.We have shown that the Ngb structure was strongly dependant on the presence of the distal histidine, the disulfide bridge and the haem environment. The first and unique determination of variants’ molar absorption…

Advisors/Committee Members: Sebban, Pierre (thesis director).

Subjects/Keywords: Neuroglobine; Mutagénèse dirigée; Cinétique de réaction; Neuroglobin; Site-directed mutagenesis; Ligang binding kinetics

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APA (6^th Edition):

André, E. (2017). Étude de l’influence de modifications structurales sur la neuroglobine humaine : Study of the influence of structural modifications on the human neuroglobin. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2017SACLS145

Chicago Manual of Style (16^th Edition):

André, Éric. “Étude de l’influence de modifications structurales sur la neuroglobine humaine : Study of the influence of structural modifications on the human neuroglobin.” 2017. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed February 27, 2021. http://www.theses.fr/2017SACLS145.

MLA Handbook (7^th Edition):

André, Éric. “Étude de l’influence de modifications structurales sur la neuroglobine humaine : Study of the influence of structural modifications on the human neuroglobin.” 2017. Web. 27 Feb 2021.

Vancouver:

André E. Étude de l’influence de modifications structurales sur la neuroglobine humaine : Study of the influence of structural modifications on the human neuroglobin. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2017. [cited 2021 Feb 27]. Available from: http://www.theses.fr/2017SACLS145.

Council of Science Editors:

André E. Étude de l’influence de modifications structurales sur la neuroglobine humaine : Study of the influence of structural modifications on the human neuroglobin. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2017. Available from: http://www.theses.fr/2017SACLS145

18. Joly, Sister Stephen Patrick. Identification of SUP5: A Protein that Interfaces with the Deviant ATP-Binding Site of the Yeast Pdr5 Multidrug Transporter.

Degree: 2018, The Catholic University of America

URL: http://hdl.handle.net/1961/cuislandora:213559

► ATP-binding cassette (ABC) transporters are present in all known organisms and comprise one of the largest families of integral membrane proteins. Clinically, ABC transporters are… (more)

▼ ATP-binding cassette (ABC) transporters are present in all known organisms and comprise one of the largest families of integral membrane proteins. Clinically, ABC transporters are associated with numerous diseases, cause multidrug resistance in various types of cancer, and cause antifungal resistance in pathogenic yeasts. Pdr5 is a plasma membrane bound multidrug transporter and the founding member of the Pdr subfamily of ABC transporters.In ABC transporters, the nucleotide binding domains dimerize to form two nucleotide binding sites, which are composed of highly conserved motifs. The deviant ATP-binding site, a unique feature of the Pdr subfamily, has been found to transmit signals between the various domains of Pdr5, specifically through the Q- loop (Ananthaswamy et al. 2010) and D-loop (Furman et al. 2013) motifs, and to facilitate ATP hydrolysis at its canonical ATP-binding site (Gupta et al. 2014). A Pdr5 deviant signature mutant, E1013A has reduced drug resistance, drug transport capability, and ATPase activity. In order to elucidate the role of the deviant signature motif, we isolated suppressors of E1013A. Two suppressors, SUP5 and SUP6, exhibited dominant gain-of-function phenotypes that significantlyrestored E1013A drug resistance independent of overexpressing Pdr5. Sup5 suppression fully restored the ATPase activity of Pdr5, while Sup6 suppression occurred via a different mechanism. Significantly, Sup5 and Sup6 were unable to rescue the loss-of-function phenotype present in the canonical signature mutant, G312A, suggesting that both are extragenic suppressors that interact specifically with the deviant ATP-binding site of Pdr5.We verified and characterized the drug resistance phenotype, ATPase activity, and plasma membrane abundance of Pdr5 for SUP5 and SUP6. Several genetic mapping and screening methods were utilized to identify SUP5 and SUP6, but a successful Yep24 overexpression screen identified SKS1, a putative serine/threonine kinase. The overexpression of SKS1 in the E1013A mutant strain mediated multidrug resistance to clotrimazole and cerulenin, possibly by phosphorylating the linker 2 region of Pdr5 (Johnson et al. 2014). Sks1-mediated phosphorylation also conferred hyper-resistance to WT Pdr5 in a manner that did not increase the ATPase activity or increase the abundance of Pdr5 in the plasma membrane. A Sks1 K39I mutation was unable to suppress the E1013A mutant. Despite common expectations, knocking out SKS1 in WT had no decrease in drug resistance, which suggests that Sks1 is not essential for Pdr5-mediated drug resistance.We proposed a mechanism for in vivo regulation of Pdr5 in low glucose and potential drug conditions based on evidence that positions Sks1 in the cAMP-PKA pathway, a pathway that controls cell division and stress responses. Sks1 has a homolog, SHA3, in C. albicans which functions in the cAMP-PKA pathway and is required for hyphal development and virulence. An SKS1 homolog, SNFK, was also found in humans, thus providing greater relevance for elucidating the Sks1 signaling… Advisors/Committee Members: The Catholic University of America (Degree granting institution), Golin, John (Thesis advisor), Corsi, Ann (Committee member), Choy, John (Committee member).

Subjects/Keywords: ABC Transporters; deviant ATP-binding site; Multidrug Resistance; Pdr5; SKS1; yeast genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Joly, S. S. P. (2018). Identification of SUP5: A Protein that Interfaces with the Deviant ATP-Binding Site of the Yeast Pdr5 Multidrug Transporter. (Thesis). The Catholic University of America. Retrieved from http://hdl.handle.net/1961/cuislandora:213559

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Joly, Sister Stephen Patrick. “Identification of SUP5: A Protein that Interfaces with the Deviant ATP-Binding Site of the Yeast Pdr5 Multidrug Transporter.” 2018. Thesis, The Catholic University of America. Accessed February 27, 2021. http://hdl.handle.net/1961/cuislandora:213559.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Joly, Sister Stephen Patrick. “Identification of SUP5: A Protein that Interfaces with the Deviant ATP-Binding Site of the Yeast Pdr5 Multidrug Transporter.” 2018. Web. 27 Feb 2021.

Vancouver:

Joly SSP. Identification of SUP5: A Protein that Interfaces with the Deviant ATP-Binding Site of the Yeast Pdr5 Multidrug Transporter. [Internet] [Thesis]. The Catholic University of America; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1961/cuislandora:213559.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Joly SSP. Identification of SUP5: A Protein that Interfaces with the Deviant ATP-Binding Site of the Yeast Pdr5 Multidrug Transporter. [Thesis]. The Catholic University of America; 2018. Available from: http://hdl.handle.net/1961/cuislandora:213559

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston College

19. Lee, Hyelee. Site-Selective Reactions Via Scaffolding Catalysis & Synthesis and Binding Study of 1,2-Azaborines.

Degree: PhD, Chemistry, 2017, Boston College

URL: http://dlib.bc.edu/islandora/object/bc-ir:107562

► Chapter 1. In the Tan laboratory, we developed synthetic methods to control reaction selectivity (regio-, stereo-, and site-selectivity) using scaffolding catalysis. Our strategy utilizes directing… (more)

▼ Chapter 1. In the Tan laboratory, we developed synthetic methods to control reaction selectivity (regio-, stereo-, and site-selectivity) using scaffolding catalysis. Our strategy utilizes directing groups that induce intramolecularity through the formation of a labile covalent bond between the substrate and a binding site in a catalytic system. In the first part, we described site-selective functionalization of various carbohydrates and complex polyhydroxylated molecules which contain cis-1,2-diol motif using a chiral organic scaffold. In the second part, meta-selective C–H functionalization of arenes was demonstrated. High meta-selectivity was achieved by the use of a nitrile-based silyl tether which is cleavable and recyclable. Chapter 2. In the Liu laboratory, we focuses on studies of boron-nitrogen containing heterocycles. In this chapter, synthesis of 1,2-azaborines and their binding study with T4 lysozyme mutants were described. Specifically, we directly compared binding of NH-containing 1,2-azaborines and their carbonaceous analogs to probe hydrogen bonding interaction between the NH group of azaborine and a carbonyl oxygen of protein residue. Structural and thermodynamic analysis provided us the first evidence of H-bonding of azaborines with a biological macromolecule. Chapter 3. Described are the synthesis of regioisomers of ethyl-substituted 1,2-azaborines and their binding thermodynamics to T4 lysozyme mutants. To access the azaborine ligands used in the binding study, we developed synthetic methods for regioselective functionalization of six positions of 1,2-azaborines. Isothermal titration calorimetry experiments showed differences in binding free energy for regioisomers to the L99A T4 lysozyme. This result could originate from electronic differences of the isosteric ligands inducing dipole-dipole interaction between ligand and surrounding protein residues or it may be from local dipolar interactions. Chapter 4. A general method for late-stage N-functionalization of 1,2-azaborines is described to afford libraries of BN-containing complex molecules. The chemical transformations include electrophilic substitution reactions, N–C(sp2) bond forming reactions under Buchwald-Hartwig amination conditions, and N–C(sp) bond forming reactions using copper-catalyzed N-alkynylation. As applications in materials science and medicinal chemistry, synthesis of the first parental BN isostere of trans-stilbene and lisdexamfetamine derivative is described utilizing the methodology developed in this work. Advisors/Committee Members: Kian L. Tan (Thesis advisor), Shih-Yuan Liu (Thesis advisor).

Subjects/Keywords: 1,2-azaborines; Binding study; C-H activation; Scaffolding catalysis; Site-selectivity; T4 lysozyme

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lee, H. (2017). Site-Selective Reactions Via Scaffolding Catalysis & Synthesis and Binding Study of 1,2-Azaborines. (Doctoral Dissertation). Boston College. Retrieved from http://dlib.bc.edu/islandora/object/bc-ir:107562

Chicago Manual of Style (16^th Edition):

Lee, Hyelee. “Site-Selective Reactions Via Scaffolding Catalysis & Synthesis and Binding Study of 1,2-Azaborines.” 2017. Doctoral Dissertation, Boston College. Accessed February 27, 2021. http://dlib.bc.edu/islandora/object/bc-ir:107562.

MLA Handbook (7^th Edition):

Lee, Hyelee. “Site-Selective Reactions Via Scaffolding Catalysis & Synthesis and Binding Study of 1,2-Azaborines.” 2017. Web. 27 Feb 2021.

Vancouver:

Lee H. Site-Selective Reactions Via Scaffolding Catalysis & Synthesis and Binding Study of 1,2-Azaborines. [Internet] [Doctoral dissertation]. Boston College; 2017. [cited 2021 Feb 27]. Available from: http://dlib.bc.edu/islandora/object/bc-ir:107562.

Council of Science Editors:

Lee H. Site-Selective Reactions Via Scaffolding Catalysis & Synthesis and Binding Study of 1,2-Azaborines. [Doctoral Dissertation]. Boston College; 2017. Available from: http://dlib.bc.edu/islandora/object/bc-ir:107562

University of Cambridge

20. Tanramluk, Duangrudee. On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine.

Degree: PhD, 2010, University of Cambridge

URL: http://www.dspace.cam.ac.uk/handle/1810/224844https://www.repository.cam.ac.uk/bitstream/1810/224844/4/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/7/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/5/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/8/PhDThesis_Kinase_TanramlukD.pdf.jpg

► Protein kinases are important regulatory enzymes in signal transduction and in cell regulation. Understanding inhibition mechanisms of kinases is important for the further development of… (more)

Subjects/Keywords: Kinase; Staurosporine; ATP binding site; Structural analysis; Selectivity; Promiscuity; Inhibitor design; Shape comparison

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tanramluk, D. (2010). On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine. (Doctoral Dissertation). University of Cambridge. Retrieved from http://www.dspace.cam.ac.uk/handle/1810/224844https://www.repository.cam.ac.uk/bitstream/1810/224844/4/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/7/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/5/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/8/PhDThesis_Kinase_TanramlukD.pdf.jpg

Chicago Manual of Style (16^th Edition):

Tanramluk, Duangrudee. “On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine.” 2010. Doctoral Dissertation, University of Cambridge. Accessed February 27, 2021. http://www.dspace.cam.ac.uk/handle/1810/224844https://www.repository.cam.ac.uk/bitstream/1810/224844/4/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/7/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/5/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/8/PhDThesis_Kinase_TanramlukD.pdf.jpg.

MLA Handbook (7^th Edition):

Tanramluk, Duangrudee. “On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine.” 2010. Web. 27 Feb 2021.

Vancouver:

Tanramluk D. On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine. [Internet] [Doctoral dissertation]. University of Cambridge; 2010. [cited 2021 Feb 27]. Available from: http://www.dspace.cam.ac.uk/handle/1810/224844https://www.repository.cam.ac.uk/bitstream/1810/224844/4/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/7/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/5/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/8/PhDThesis_Kinase_TanramlukD.pdf.jpg.

Council of Science Editors:

Tanramluk D. On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine. [Doctoral Dissertation]. University of Cambridge; 2010. Available from: http://www.dspace.cam.ac.uk/handle/1810/224844https://www.repository.cam.ac.uk/bitstream/1810/224844/4/license.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/7/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/5/PhDThesis_Kinase_TanramlukD.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/224844/8/PhDThesis_Kinase_TanramlukD.pdf.jpg

George Mason University

21. Hosseini, Parsa. Quantifying the Glycine max Proximal Cis-regulome during Pathogenesis.

Degree: 2013, George Mason University

URL: http://hdl.handle.net/1920/8778

► Transcription regulation is a highly orchestrated dynamic which mediates every aspect of organismal development. Following host perception of positive or negative stress, hormone-driven signaling amplifies… (more)

Subjects/Keywords: Bioinformatics; Glycine max; Soybean cyst nematode; Soybean rust; Transcription factor binding site

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APA (6^th Edition):

Hosseini, P. (2013). Quantifying the Glycine max Proximal Cis-regulome during Pathogenesis. (Thesis). George Mason University. Retrieved from http://hdl.handle.net/1920/8778

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hosseini, Parsa. “Quantifying the Glycine max Proximal Cis-regulome during Pathogenesis. ” 2013. Thesis, George Mason University. Accessed February 27, 2021. http://hdl.handle.net/1920/8778.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hosseini, Parsa. “Quantifying the Glycine max Proximal Cis-regulome during Pathogenesis. ” 2013. Web. 27 Feb 2021.

Vancouver:

Hosseini P. Quantifying the Glycine max Proximal Cis-regulome during Pathogenesis. [Internet] [Thesis]. George Mason University; 2013. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1920/8778.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hosseini P. Quantifying the Glycine max Proximal Cis-regulome during Pathogenesis. [Thesis]. George Mason University; 2013. Available from: http://hdl.handle.net/1920/8778

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia Tech

22. Hassanzadeh, Hamid Reza. Advanced Machine Learning Approaches for Characterization of Transcriptional Regulatory Elements and Genome-Wide Associations.

Degree: PhD, Interactive Computing, 2020, Georgia Tech

URL: http://hdl.handle.net/1853/62784

► The deep learning revolution has initiated a surge of remarkable achievements in diverse research areas where large volumes of data that underlie complex processes exist.… (more)

▼ The deep learning revolution has initiated a surge of remarkable achievements in diverse research areas where large volumes of data that underlie complex processes exist. Despite the successful application of deep models in solving certain problems in the Biomedical and Bioinformatics domains, the field has not brought any promise in solving many other challenging problems that deal with the genomic complexities. The goal of my Ph.D. research has been to develop advanced machine learning techniques to address two relevant challenging problems in the Bioinformatics domain, namely, the characterization of transcriptional regulatory elements and, modeling genome-wide associations and linkage disequilibrium using genomic and evolutionary annotation of variants. Genome codes for almost all biological phenomena that take place inside living cells. One such key interactions is the association between transcription factors and a number of degenerate binding sites on DNA which facilitate initiation of transcription of genes. While each protein can potentially bind to any site on the DNA, it is the strength of this binding that plays the key role in the initiation process. Predicting these binding sites as well as binding affinities, are two interesting and yet challenging problems that remain largely unsolved. Yet, we know that the cell machineries constantly identify such sites on DNA with near perfect accuracy. The last two decade witnessed production of multiple in-vivo and in-vitro high-throughput technologies for elucidating these interactions. Protein Binding Microarrays (PBM) have been one of the most effective in-vitro technologies developed so far. The result of PBM experiments, however, are not easily interpretable and require advanced downstream analysis tools to discover the patterns of bindings. In the first half of my thesis, I will develop a series of computational methods that can learn such patterns from data generated by this technology, using tools and techniques from the natural language and image processing domains. I will also show the superiority of my proposed pipelines in predicting binding patterns and affinity. The second part of my thesis is devoted to developing methods for modeling of genome-wide associations and the linkage disequilibrium. Both of these tasks pose similar challenges that restrict our ability in utilizing recent advances in deep learning research. Specifically, when dealing with GWA studies, we are often bound by high dimensionality of variants data, a significant degree of missing information (i.e. missing heritability), high complexity weak patterns to learn, and relatively small datasets. As a consequence, the state-of-the-art approaches for GWAS that are used in practice are different variations of linear models. In my thesis, I showed that part of the failure in learning higher-capacity models can be attributed to how we are training such models. Specifically, I showed that using Siamese networks and tools from graph theory we can achieve a performance higher or on par… Advisors/Committee Members: Isbell, Chales (advisor), Gibson, Gregory (advisor), Qiu, Peng (committee member), Dovorolis, Constantine (committee member), Tsygankvo, Denis (committee member).

Subjects/Keywords: Deep Learning; Genome-Wide Association Studies (GWAS); Transcription Factor Binding Site Modeling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hassanzadeh, H. R. (2020). Advanced Machine Learning Approaches for Characterization of Transcriptional Regulatory Elements and Genome-Wide Associations. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62784

Chicago Manual of Style (16^th Edition):

Hassanzadeh, Hamid Reza. “Advanced Machine Learning Approaches for Characterization of Transcriptional Regulatory Elements and Genome-Wide Associations.” 2020. Doctoral Dissertation, Georgia Tech. Accessed February 27, 2021. http://hdl.handle.net/1853/62784.

MLA Handbook (7^th Edition):

Hassanzadeh, Hamid Reza. “Advanced Machine Learning Approaches for Characterization of Transcriptional Regulatory Elements and Genome-Wide Associations.” 2020. Web. 27 Feb 2021.

Vancouver:

Hassanzadeh HR. Advanced Machine Learning Approaches for Characterization of Transcriptional Regulatory Elements and Genome-Wide Associations. [Internet] [Doctoral dissertation]. Georgia Tech; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1853/62784.

Council of Science Editors:

Hassanzadeh HR. Advanced Machine Learning Approaches for Characterization of Transcriptional Regulatory Elements and Genome-Wide Associations. [Doctoral Dissertation]. Georgia Tech; 2020. Available from: http://hdl.handle.net/1853/62784

23. Wong, Ka Chun. Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors.

Degree: PhD, 2015, University of Toronto

URL: http://hdl.handle.net/1807/69051

► The protein-DNA interactions between Transcription Factors (TFs) and Transcription Factor Binding Sites (TFBSs) are the key activities in gene regulation. Considerable efforts have been spent… (more)

▼ The protein-DNA interactions between Transcription Factors (TFs) and Transcription Factor Binding Sites (TFBSs) are the key activities in gene regulation. Considerable efforts have been spent on elucidating their binding mechanisms in the past twenty years. In this thesis, I propose and describe three methods to learn and predict the DNA binding specificities of TFs.The first method named kmerHMM is a sequence pattern recognition method to discover the sequence patterns of TFBSs from protein binding microarray (PBM) data. The novelty of kmerHMM lies in two aspects. First, it has a competitive edge over the existing methods in using Hidden Markov Models (HMMs) to derive an HMM model to represent PBM data. Secondly, kmerHMM incorporates N-Max-Product algorithm and can derive multiple motif matrix models to represent PBM data. The second method named SNPdryad is a classification method to predict the deleterious effect of amino acid substitutions on proteins (including TFs). Comprehensive performance comparisons are conducted on benchmark datasets, reflecting that SNPdryad has the performance comparable to the best of the other methods. SNPdryad has been run on the complete human proteome, generating prediction scores for all the possible amino acid substitutions. In particular, case studies are conducted to show that SNPdryad can help identify the deleterious effect on TFs if a DNA-binding residue is mutated to others.The third method is a computational framework to learn specificity-determining pair-wise residue and nucleotide interactions between TFs and TFBSs. Its novelty lies in the fact that the existing methods usually focus on learning DNA-binding residues on the protein side (TF) only, ignoring the DNA side (TFBS). In contrast, our novel framework aims at learning the interactions between both sides. The proposed method is compared to state-of-the-art methods comprehensively, demonstrating its competitive performance. We also describe case studies showing how our method can be applied to reveal meaningful biological insights into protein-DNA interactions across different DNA-binding families. Advisors/Committee Members: Zhang, Zhaolei, Computer Science.

Subjects/Keywords: Data Mining; DNA Binding Site; Gene Regulation; Machine Learning; Sequence Analysis; Transcription Factor; 0984

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wong, K. C. (2015). Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/69051

Chicago Manual of Style (16^th Edition):

Wong, Ka Chun. “Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors.” 2015. Doctoral Dissertation, University of Toronto. Accessed February 27, 2021. http://hdl.handle.net/1807/69051.

MLA Handbook (7^th Edition):

Wong, Ka Chun. “Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors.” 2015. Web. 27 Feb 2021.

Vancouver:

Wong KC. Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1807/69051.

Council of Science Editors:

Wong KC. Computational Methods for Learning and Predicting the DNA binding Specificities of Transcription Factors. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/69051

Washington University in St. Louis

24. Sahota, Gurmukh. Novel Sequence-Based Method for Identifying Transcription Factor Binding Sites in Prokaryotic Genomes.

Degree: PhD, Biology and Biomedical Sciences: Computational and Systems Biology, 2012, Washington University in St. Louis

URL: https://openscholarship.wustl.edu/etd/636

► Computational techniques for microbial genomic sequence analysis are becoming increasingly important. With next–generation sequencing technology and the human microbiome project underway, current sequencing capacity is… (more)

▼ Computational techniques for microbial genomic sequence analysis are becoming increasingly important. With next–generation sequencing technology and the human microbiome project underway, current sequencing capacity is significantly greater than the speed at which organisms of interest can be experimentally probed. We have developed a method that will primarily use available sequence data in order to determine prokaryotic transcription factor binding specificities. The prototypical prokaryotic transcription factor: TF) contains a helix–turn–helix: HTH) fold and bind DNA as homodimers, leading to their palindromic motif specificities. The connection between the TF and its promoter is based on the autoregulation phenomenon noticed in E. coli. Approximately 55% of the TFs analyzed were estimated to be autoregulated. Our preliminary analysis using RegulonDB indicates that this value increases to 79% if one considers the neighboring operons. Given the TF family of interest, it is necessary to find the relevant TF proteins and their associated genomes. Due to the scale–free network topology of prokaryotic systems, many of the transcriptional regulators regulate only one or a few operons. Within a single genome, there would not be enough sequence–based signal to determine the binding site using standard computational methods. Therefore, multiple bacterial genomes are used to overcome this lack of signal within a single genome. We use a distance–based criteria to define the operon boundaries and their respective promoters. Several TF–DNA crystal structures are then used to determine the residues that interact with the DNA. These key residues are the basis for the TF comparison metric; the assumption being that similar residues should impart similar DNA binding specificities. After defining the sets of TF clusters using this metric, their respective promoters are used as input to a motif finding procedure. This method has currently been tested on the LacI and TetR TF families with successful results. On external validation sets, the specificity of prediction is ∼80%. These results are important in developing methods to define the DNA binding preferences of the TF protein residues, known as the “recognition code”. This “recognition code” would allow computational design and prediction of novel DNA–binding specificities, enabling protein-engineering and synthetic biology applications. Advisors/Committee Members: Gary Stormo.

Subjects/Keywords: Bioinformatics; Microbiology; Systematic biology; Binding site; Large-scale data analysis; Motif; Prokaryotic; Sequencing; Transcription factor

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APA (6^th Edition):

Sahota, G. (2012). Novel Sequence-Based Method for Identifying Transcription Factor Binding Sites in Prokaryotic Genomes. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/636

Chicago Manual of Style (16^th Edition):

Sahota, Gurmukh. “Novel Sequence-Based Method for Identifying Transcription Factor Binding Sites in Prokaryotic Genomes.” 2012. Doctoral Dissertation, Washington University in St. Louis. Accessed February 27, 2021. https://openscholarship.wustl.edu/etd/636.

MLA Handbook (7^th Edition):

Sahota, Gurmukh. “Novel Sequence-Based Method for Identifying Transcription Factor Binding Sites in Prokaryotic Genomes.” 2012. Web. 27 Feb 2021.

Vancouver:

Sahota G. Novel Sequence-Based Method for Identifying Transcription Factor Binding Sites in Prokaryotic Genomes. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2012. [cited 2021 Feb 27]. Available from: https://openscholarship.wustl.edu/etd/636.

Council of Science Editors:

Sahota G. Novel Sequence-Based Method for Identifying Transcription Factor Binding Sites in Prokaryotic Genomes. [Doctoral Dissertation]. Washington University in St. Louis; 2012. Available from: https://openscholarship.wustl.edu/etd/636

Duke University

25. Georgiev, Stoyan. Computational Methods For Functional Motif Identification and Approximate Dimension Reduction in Genomic Data .

Degree: 2011, Duke University

URL: http://hdl.handle.net/10161/5708

► Uncovering the DNA regulatory logic in complex organisms has been one of the important goals of modern biology in the post-genomic era. The sequencing… (more)

Subjects/Keywords: Bioinformatics; binding site; chip-seq; dimension reduction; population structure; randomized algorithm; transcription factor

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APA (6^th Edition):

Georgiev, S. (2011). Computational Methods For Functional Motif Identification and Approximate Dimension Reduction in Genomic Data . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/5708

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Georgiev, Stoyan. “Computational Methods For Functional Motif Identification and Approximate Dimension Reduction in Genomic Data .” 2011. Thesis, Duke University. Accessed February 27, 2021. http://hdl.handle.net/10161/5708.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Georgiev, Stoyan. “Computational Methods For Functional Motif Identification and Approximate Dimension Reduction in Genomic Data .” 2011. Web. 27 Feb 2021.

Vancouver:

Georgiev S. Computational Methods For Functional Motif Identification and Approximate Dimension Reduction in Genomic Data . [Internet] [Thesis]. Duke University; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10161/5708.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Georgiev S. Computational Methods For Functional Motif Identification and Approximate Dimension Reduction in Genomic Data . [Thesis]. Duke University; 2011. Available from: http://hdl.handle.net/10161/5708

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

26. Impellizzeri, Agata Antonina Rita. Site-directed mutagenesis and molecular modeling studies of h5-HT7(a) receptor reveal important residues for binding and activation.

Degree: 2012, Università degli Studi di Catania

URL: http://hdl.handle.net/10761/1169

► Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter implicated in neuropsychiatric disturbance such as depression, anxiety and psychosis. Recent studies on knockout animals and using selective… (more)

Subjects/Keywords: Area 05 - Scienze biologiche; 5-HT7(a) serotonin receptor, site-directed mutagenesis, binding, activation

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APA (6^th Edition):

Impellizzeri, A. A. R. (2012). Site-directed mutagenesis and molecular modeling studies of h5-HT7(a) receptor reveal important residues for binding and activation. (Thesis). Università degli Studi di Catania. Retrieved from http://hdl.handle.net/10761/1169

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Impellizzeri, Agata Antonina Rita. “Site-directed mutagenesis and molecular modeling studies of h5-HT7(a) receptor reveal important residues for binding and activation.” 2012. Thesis, Università degli Studi di Catania. Accessed February 27, 2021. http://hdl.handle.net/10761/1169.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Impellizzeri, Agata Antonina Rita. “Site-directed mutagenesis and molecular modeling studies of h5-HT7(a) receptor reveal important residues for binding and activation.” 2012. Web. 27 Feb 2021.

Vancouver:

Impellizzeri AAR. Site-directed mutagenesis and molecular modeling studies of h5-HT7(a) receptor reveal important residues for binding and activation. [Internet] [Thesis]. Università degli Studi di Catania; 2012. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10761/1169.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Impellizzeri AAR. Site-directed mutagenesis and molecular modeling studies of h5-HT7(a) receptor reveal important residues for binding and activation. [Thesis]. Università degli Studi di Catania; 2012. Available from: http://hdl.handle.net/10761/1169

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Edinburgh

27. Joshi, Akshay. Editing the mouse genome to understand the regulation of milk proteins.

Degree: PhD, 2019, University of Edinburgh

URL: http://hdl.handle.net/1842/36148

► Dairy industries not only contribute to global food security but also have a major economic role worldwide. Milk is an important source of proteins, lactose,… (more)

Subjects/Keywords: casein locus; STAT5; CRISPRs; HC11 cells; lalba promoter; STAT5 tetramer transcription factor binding site

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APA (6^th Edition):

Joshi, A. (2019). Editing the mouse genome to understand the regulation of milk proteins. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/36148

Chicago Manual of Style (16^th Edition):

Joshi, Akshay. “Editing the mouse genome to understand the regulation of milk proteins.” 2019. Doctoral Dissertation, University of Edinburgh. Accessed February 27, 2021. http://hdl.handle.net/1842/36148.

MLA Handbook (7^th Edition):

Joshi, Akshay. “Editing the mouse genome to understand the regulation of milk proteins.” 2019. Web. 27 Feb 2021.

Vancouver:

Joshi A. Editing the mouse genome to understand the regulation of milk proteins. [Internet] [Doctoral dissertation]. University of Edinburgh; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/1842/36148.

Council of Science Editors:

Joshi A. Editing the mouse genome to understand the regulation of milk proteins. [Doctoral Dissertation]. University of Edinburgh; 2019. Available from: http://hdl.handle.net/1842/36148

28. Γεωργοπούλου, Αικατερίνη. Χαρτογράφηση του κέντρου δέσμευσης και μεταφοράς πουρινών των μεταφορέων νουκλεοτιδικών βάσεων-ασκορβικού (ΝΑΤ).

Degree: 2011, University of Ioannina; Πανεπιστήμιο Ιωαννίνων

URL: http://hdl.handle.net/10442/hedi/34765

► The nucleobase-ascorbate transporter (NAT) family is an evolutionarily broad family of nucleobase-ascorbate transporters with more than 2000 putative members based on genome programs from all… (more)

▼ The nucleobase-ascorbate transporter (NAT) family is an evolutionarily broad family of nucleobase-ascorbate transporters with more than 2000 putative members based on genome programs from all organisms. Only few members of this family have been characterized and only two of them, the specific xanthine transporter XanQ from E. coli and the uric acid/xanthine transporter UapA from Aspergillus nidulans, have been studied extensively at the molecular level. Lately, the x-ray structure of another member of this family, the uracil transporter UraA, has been solved at high resolution, providing a model of how all transporters from this family are structurally organized. As a study model we use the recently cloned and functionally characterized XanQ transporter from E. coli K12, a specific, high-affinity xanthine: Η+ symporter. In the present thesis, we analyze the role of some of important residues with respect to their putative direct or indirect involvement with the substrate binding site of XanQ. We performed site-directed alkylation and functional assays of single-Cys mutants of the NAT motif and flanking regions, in the presence or absence of xanthine. The experiments indicate that two of the NAT motif residues interact directly with the xanthine binding site, Asn-325 and Gln-324 while the neighboring Ala-323 responds with a small conformational change which causes an increased sensitivity to inactivation. Moreover, residues 326-329 and residues at positions 332, 333 and 336 appear to participate in the purine permeation pathway. In the second part of the thesis, we studied the role of the C-terminal TM of XanQ. The revised model of XanQ based on the crystal structure of UraA shows that the C-terminal TM is distant from the binding site and its interaction with the NAT motif should be indirect. In the present thesis, engineering of chimera N11C1 and its “resurrection” through rational mutagenesis steps has revealed important elements for the function and evolution of XanQ which were not discernible in the previous studies. In particular, Asn-430 and Ile-432, located at the middle of this TM at the beginning of the last small alpha helix (α14), are crucial for the right conformation and expression of the transporter in the membrane, the length of the extended unstructured loop between the last two alpha helices (α13 and α14) is crucial for high xanthine uptake activity since deletion of 11 residues from this sequence is needed to restore full uptake activity in chimera N11C1. Restoration of the correct XanQ specificity, especially with respect to the non-recognition of uric acid, 7-methylxanthine and 8-methylxanthine, requires the additional re-introduction of two glycines, Gly-435 and Gly-436, in the middle of α14, while any combination of the other mutations lead to chimeras with high promiscuity for recognition of these non-XanQ ligands. The above series of mutations leads to the rebuilt of a chimera which is functionally equivalent to wild-type XanQ in terms of activity and specificity. In addition, these data are…

Subjects/Keywords: Μεταφορείς NAT; Κέντρο δέσμευσης πουρινών; Ξανθίνη; NAT transporters; Purine binding site; Xanthine

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APA (6^th Edition):

Γεωργοπούλου, . �. (2011). Χαρτογράφηση του κέντρου δέσμευσης και μεταφοράς πουρινών των μεταφορέων νουκλεοτιδικών βάσεων-ασκορβικού (ΝΑΤ). (Thesis). University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Retrieved from http://hdl.handle.net/10442/hedi/34765

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Γεωργοπούλου, Αικατερίνη. “Χαρτογράφηση του κέντρου δέσμευσης και μεταφοράς πουρινών των μεταφορέων νουκλεοτιδικών βάσεων-ασκορβικού (ΝΑΤ).” 2011. Thesis, University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Accessed February 27, 2021. http://hdl.handle.net/10442/hedi/34765.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Γεωργοπούλου, Αικατερίνη. “Χαρτογράφηση του κέντρου δέσμευσης και μεταφοράς πουρινών των μεταφορέων νουκλεοτιδικών βάσεων-ασκορβικού (ΝΑΤ).” 2011. Web. 27 Feb 2021.

Vancouver:

Γεωργοπούλου �. Χαρτογράφηση του κέντρου δέσμευσης και μεταφοράς πουρινών των μεταφορέων νουκλεοτιδικών βάσεων-ασκορβικού (ΝΑΤ). [Internet] [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10442/hedi/34765.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Γεωργοπούλου �. Χαρτογράφηση του κέντρου δέσμευσης και μεταφοράς πουρινών των μεταφορέων νουκλεοτιδικών βάσεων-ασκορβικού (ΝΑΤ). [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2011. Available from: http://hdl.handle.net/10442/hedi/34765

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

29. Ngo, Tony. Drug discovery at the orphan G protein-coupled receptor, GPR37L1.

Degree: Victor Chang Cardiac Research Institute, 2017, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/57884 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:45053/SOURCE02?view=true

► Over 100 orphan G protein-coupled receptors (GPCRs) are yet to be paired with their endogenous ligand. As such, they represent a vast untapped resource for… (more)

▼ Over 100 orphan G protein-coupled receptors (GPCRs) are yet to be paired with their endogenous ligand. As such, they represent a vast untapped resource for drug discovery. Therefore, identifying ligands for these orphan receptors is crucial for the exploration of their physiological and pharmacological relevance. One such orphan is GPR37L1, a potential mediator of cardiovascular homeostasis. In this thesis, GPR37L1 was found to be predominantly a constitutively active Gαs-coupled receptor and that metalloprotease cleavage of GPR37L1’s N-terminus regulated its signalling capabilities. This thesis also introduced GPCR-CoINPocket, a new method for orphan receptor ligand discovery. GPCR-CoINPocket (Contact-Informed Neighbouring Pocket) was first designed to improve recognition of known pharmacological similarities, or off-target activity amongst Class A GPCRs from a binding pocket perspective. This was achieved by focusing on specific residue positions in the ligand binding pocket that were interaction hotspots, as observed in crystallographically-characterised GPCRs. This was extended to prospectively predict binding site-similar receptors for all orphan receptors, including GPR37L1. GPCR-CoINPocket predicted the bombesin, orexin and neuropeptide S receptors to be most similar to GPR37L1, and not the phylogenetically related endothelin receptors, which guided and narrowed the search for GPR37L1 surrogate ligands. Other approaches were also used to identify GPR37L1 ligands, including traditional ligand screening and in silico ligand screening with an unrefined GPR37L1 homology model. The surrogate ligands identified with these various approaches will provide the necessary stepping-stone to explore the therapeutic potential of GPR37L1; the identified ligands can now be used to refine homology models for a second iteration of virtual ligand screening, as well as facilitate parallel in vitro and in vivo studies. The endogenous ligand for GPR37L1 remains elusive. Advisors/Committee Members: Smith, Nicola, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW, Graham, Robert, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW, Abagyan, Ruben, Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego.

Subjects/Keywords: Computational biology; Orphan G protein-coupled receptor; Ligand discovery; Binding site comparisons

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APA (6^th Edition):

Ngo, T. (2017). Drug discovery at the orphan G protein-coupled receptor, GPR37L1. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/57884 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:45053/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Ngo, Tony. “Drug discovery at the orphan G protein-coupled receptor, GPR37L1.” 2017. Doctoral Dissertation, University of New South Wales. Accessed February 27, 2021. http://handle.unsw.edu.au/1959.4/57884 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:45053/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Ngo, Tony. “Drug discovery at the orphan G protein-coupled receptor, GPR37L1.” 2017. Web. 27 Feb 2021.

Vancouver:

Ngo T. Drug discovery at the orphan G protein-coupled receptor, GPR37L1. [Internet] [Doctoral dissertation]. University of New South Wales; 2017. [cited 2021 Feb 27]. Available from: http://handle.unsw.edu.au/1959.4/57884 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:45053/SOURCE02?view=true.

Council of Science Editors:

Ngo T. Drug discovery at the orphan G protein-coupled receptor, GPR37L1. [Doctoral Dissertation]. University of New South Wales; 2017. Available from: http://handle.unsw.edu.au/1959.4/57884 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:45053/SOURCE02?view=true

Ohio University

30. Wolfe, Richard A. In Silico Discovery of Pollen-specific Cis-regulatory Elements in the Arabidopsis Hydroxyproline-Rich Glycoprotein Gene Family.

Degree: MS, Computer Science (Engineering and Technology), 2014, Ohio University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1408383003

► Within every cell is a copy of an organism's DNA. This copy of DNA has all of the information needed for the cell to express… (more)

Subjects/Keywords: Bioinformatics; Computer Science; Bioinformatics; transcription factor; transcription factor binding site; motif discovery; computer

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APA (6^th Edition):

Wolfe, R. A. (2014). In Silico Discovery of Pollen-specific Cis-regulatory Elements in the Arabidopsis Hydroxyproline-Rich Glycoprotein Gene Family. (Masters Thesis). Ohio University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1408383003

Chicago Manual of Style (16^th Edition):

Wolfe, Richard A. “In Silico Discovery of Pollen-specific Cis-regulatory Elements in the Arabidopsis Hydroxyproline-Rich Glycoprotein Gene Family.” 2014. Masters Thesis, Ohio University. Accessed February 27, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1408383003.

MLA Handbook (7^th Edition):

Wolfe, Richard A. “In Silico Discovery of Pollen-specific Cis-regulatory Elements in the Arabidopsis Hydroxyproline-Rich Glycoprotein Gene Family.” 2014. Web. 27 Feb 2021.

Vancouver:

Wolfe RA. In Silico Discovery of Pollen-specific Cis-regulatory Elements in the Arabidopsis Hydroxyproline-Rich Glycoprotein Gene Family. [Internet] [Masters thesis]. Ohio University; 2014. [cited 2021 Feb 27]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1408383003.

Council of Science Editors:

Wolfe RA. In Silico Discovery of Pollen-specific Cis-regulatory Elements in the Arabidopsis Hydroxyproline-Rich Glycoprotein Gene Family. [Masters Thesis]. Ohio University; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1408383003

Open Access Theses and Dissertations