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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Prevelige, Peter<br>"). Showing records 1 – 3 of 3 total matches.

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1. Kallmeyer, Adam K. (Adam Keith). Regulatory mechanisms of eukaryotic translation termination.

Degree: PhD, 2007, University of Alabama – Birmingham

Translation is separated into three distinct steps: initiation, elongation, and termination. Termination is mediated by a heterodimer of eRF1 and eRF3. eRF1 (encoded by the SUP45 gene) functions to recognize the stop codon in the A-site of the ribosome and stimulate polypeptide chain release. eRF3 is a GTPase that helps eRF1 stimulate release. Translation consumes a large amount of resources and is highly regulated. Regulatory mechanisms exist to control translation at the first two steps. We made the novel observation that eRF1 is phosphorylated by the CK2-kinase at serines 421 and 432 suggesting that the final step of translation may also be regulated. Phosphorylation of eRF1 was found to be dynamic and dependent on active cellular metabolism. Phosphorylation played little role in mediating stop codon recognition and no role in NMD or binding to eRF3. During our studies of eRF1 phosphorylation, we made a mutant of eRF1 where the C-terminal 19 amino acids were deleted (eRF1-C[Delta]19). This mutant has a reduced affinity for eRF3 and a readthrough phenotype. In addition, the eRF1-C[Delta]19 steady-state protein and sup45-C[Delta]19 mRNA levels are elevated 5-fold by a mechanism that increases the half-life of the SUP45 transcript. We furthered our study and found that eRF1 levels were elevated in a strain expressing a GTPase deficient mutant, eRF3-H348Q, and in a strain expressing a hybrid eRF1 protein, Eo1/Sc23-eRF1- C124S. The increase in eRF1 levels was not due to a defect in stop codon recognition or a decrease in the catalytic efficiency of the GTPase activity of eRF3. We concluded our study showing that the eRF1-C[Delta]19 and eRF3-H348Q mutants have a slow rate of peptide release. When we combine these data with the cold sensitive phenotype of the Eo1/Sc23- eRF1-C124S mutant, our results indicate that steady-state levels of eRF1 are most likely coupled to a defect in polypeptide chain release. This study reveals a novel regulatory mechanism to control eRF1 levels in a eukaryote.

x, 109 p. : ill., digital, PDF file

Microbiology

Joint Health Sciences

eRF1 eRF3 Translation Termination Translation Regulation Protein Synthesis Ribosome

UNRESTRICTED

Advisors/Committee Members: Bedwell, David M., Frank, Stuart<br>Morrow, Casey<br>Prevelige, Peter<br>Steyn, Adrie.

Subjects/Keywords: Casein Kinase II  – metabolism<; br>; Peptide Termination Factors  – metabolism<; br>; Protein Biosynthesis  – physiology<; br>; Recombinant Fusion Proteins<; br>; Saccharomyces cerevisiae  – genetics<; br>; Saccharomyces cerevisiae Proteins  – metabolism

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

APA (6th Edition):

Kallmeyer, A. K. (. K. (2007). Regulatory mechanisms of eukaryotic translation termination. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,450

Chicago Manual of Style (16th Edition):

Kallmeyer, Adam K (Adam Keith). “Regulatory mechanisms of eukaryotic translation termination.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 23, 2019. http://contentdm.mhsl.uab.edu/u?/etd,450.

MLA Handbook (7th Edition):

Kallmeyer, Adam K (Adam Keith). “Regulatory mechanisms of eukaryotic translation termination.” 2007. Web. 23 Oct 2019.

Vancouver:

Kallmeyer AK(K. Regulatory mechanisms of eukaryotic translation termination. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2019 Oct 23]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,450.

Council of Science Editors:

Kallmeyer AK(K. Regulatory mechanisms of eukaryotic translation termination. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,450

2. Cook, Ian Thomas. Anaylsis [sic] of the structural and kinetic properties of human SULT2A1 induced by the binding of 3'-phosphoadenosine-5'-phosphosulfate.

Degree: PhD, 2011, University of Alabama – Birmingham

Sulfation is an important Phase II drug metabolism reaction catalyzed by the cytosolic sulfotransferases (SULTs). SULT2A1 is a major SULT in liver and adrenal cortex that has been reported to sulfate a wide variety of substrates including bile acids, steroids, and drugs. The crystal structures of SULT2A1 suggest that PAPS binding causes a structural change. This study examines the kinetic changes in SULT2A1 caused by PAPS binding using computer modeling, enzyme kinetics, binding studies, and mammalian cells expressing SULT2A1. The data presented clearly demonstrate that the binding of PAPS changes the affinity of some substrates to SULT2A1 resulting in different apparent reaction mechanisms. With small substrates, such as dehydroepiandrosterone (DHEA), the binding of PAPS causes only a small change in substrate affinity to SULT2A1. For these substrates, either PAPS or acceptor may bind first resulting in a random Bi Bi reaction mechanism. With larger substrates, the binding of PAPS generated a conformational change in SULT2A1 that blocked the substrate from binding in a catalytic orientation. In these reactions, the substrate must bind before PAPS resulting in an ordered reaction mechanism. All human SULTs have been identified as homodimers. In SULT2A1, the addition of an amino-terminal maltose binding protein (MBP) tag disrupted dimerization. The MBP-SULT2A1 monomer was kinetically active and showed similar affinities for DHEA and PAPS as the SULT2A1 homodimer. However, the MBP-SULT2A1 monomer did not show substrate inhibition. Analysis of MBP-SULT2A1 and dimeric SULT2A1 demonstrated that substrate inhibition of DHEA was caused by the binding of DHEA at an inhibitory allosteric site. The inhibitory binding site was blocked or disrupted when PAPS bound to the homodimer. The molecular rearrangements observed in SULT2A1 upon PAPS binding were hypothesized to occur in other SULT isoforms. Modeling and enzyme kinetics demonstrated that similar as well as different structural changes occur in SULT1A1. These changes had a significant effect on the binding and kinetic properties of SULT1A1 The study presents novel insights into SULT2A1 and SULT1A1 structural, kinetic, and binding properties, and provides valuable insights for improving the in silico predictions of the in vivo sulfation of therapeutic drugs.

1 online resource (xvii, 249 p.) : ill., digital, PDF file.

Pharmacology and Toxicology;

Joint Health Sciences;

Sulfotransferase Phase II drug metabolism docking 3’-phosphoadenosine-5’-phosphosulfate, dehydroepiandrosterone enzyme kinetics

UNRESTRICTED

Advisors/Committee Members: Barnes, Stephen, Falany, Charles N.<br>, Bjornsti, Mary-Ann<br>, Prevelige, Peter<br>, Song, Yuhua.

Subjects/Keywords: Cytosol  – enzymology<; br>; Enzyme Inhibitors  – pharmacology<; br>; Liver<; br>; Sulfatases  – metabolism<; br>; Sulfates  – metabolism<; br>; Sulfotransferases  – metabolism

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

APA (6th Edition):

Cook, I. T. (2011). Anaylsis [sic] of the structural and kinetic properties of human SULT2A1 induced by the binding of 3'-phosphoadenosine-5'-phosphosulfate. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1047

Chicago Manual of Style (16th Edition):

Cook, Ian Thomas. “Anaylsis [sic] of the structural and kinetic properties of human SULT2A1 induced by the binding of 3'-phosphoadenosine-5'-phosphosulfate.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 23, 2019. http://contentdm.mhsl.uab.edu/u?/etd,1047.

MLA Handbook (7th Edition):

Cook, Ian Thomas. “Anaylsis [sic] of the structural and kinetic properties of human SULT2A1 induced by the binding of 3'-phosphoadenosine-5'-phosphosulfate.” 2011. Web. 23 Oct 2019.

Vancouver:

Cook IT. Anaylsis [sic] of the structural and kinetic properties of human SULT2A1 induced by the binding of 3'-phosphoadenosine-5'-phosphosulfate. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2019 Oct 23]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1047.

Council of Science Editors:

Cook IT. Anaylsis [sic] of the structural and kinetic properties of human SULT2A1 induced by the binding of 3'-phosphoadenosine-5'-phosphosulfate. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1047

3. Gamble, Lena Jeanelle. Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins.

Degree: PhD, 2010, University of Alabama – Birmingham

Ovarian cancer is the leading cause of gynecological disease death in women. For the past two decades, scientists have attempted to perfect the use of adenovirus as an anti-cancer therapeutic agent. One major impediment to ovarian tumor infection with adenovirus has been dearth of adenovirus native receptor, Coxsackie and Adenovirus receptor, (CAR), on the surface of tumor cells. To address this problem, scientists have engineered CAR-independent adenoviruses which target the AlphavBeta3 and AlphavBeta5 by adding an arginine-glycine-aspartate (RGD) motif to the fiber knob of a conditionally replicating adenovirus (CRAd) Delta24FiberRGD CRAd. We hypothesize that incorporation of RGD into the pIX motif of the Delta24FiberRGD CRAd, resulting in a Double RGD CRAd, will have increased oncolytic capabilities in in vitro and in vivo ovarian cancer models versus Delta24FiberRGD CRAd. We produced a Double RGD CRAd (Delta24-pIXRGD-FiberRGD CRAd) by adding a motif to the pIX protein consisting of a 45angstrom linker, a Flag protein (DYKDDDDK) for subsequent verification of incorporation of pIX modification, and the RGD motif to compare its oncolytic ability with that of the previously produced Delta24FiberRGD. This virus was rendered cancer selective by deletion of 24 bases from the E1A region of the adenovirus genome. The presence of RGD motifs at both the pIX and the fiber locales as well as maintenance of the 24-base deletion in the E1 region were verified prior to in vitro and in vivo experimentation. As compared to Delta24 CRAd without RGD modifications, Delta24 CRAd with RGD motif on pIX only, and Delta24 CRAd with RGD motif on Fiber only, Double RGD CRAd showed enhanced oncoloytic ability in vitro and similar oncolytic ability in vivo in an intraperitoneal model of ovarian cancer in nude mice. These data indicate that a viable and oncolytically-enhanced virus may be produced by addition of RGD motifs to both the pIX and fiber motifs of the adenovirus capsid. This strategy provides evidence for the effective use of the pIX protein which may be used in future gene therapy or virotherapy applications that require modification of Ad serotype 5.

PhD

1 online resource (x, 92 p.) :ill., digital, PDF file.

Pathology

Health Professions

Adenovirus CRAd ovarian cancer RGD

UNRESTRICTED

Advisors/Committee Members: David T. Curiel, Goepfert,Paul Lorenz,Robin Prevelige,Peter Siegal,Gene Smith,Bruce.

Subjects/Keywords: Adipose Tissue<; br>; Body Fat Distribution.<; br>; Insulin Resistance<; br>; Intra-Abdominal Fat.<; br>; Muscle, Skeletal<; br>; Postmenopause<; br>; Thigh

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Gamble, L. J. (2010). Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,1400

Chicago Manual of Style (16th Edition):

Gamble, Lena Jeanelle. “Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins.” 2010. Doctoral Dissertation, University of Alabama – Birmingham. Accessed October 23, 2019. http://contentdm.mhsl.uab.edu/u?/etd,1400.

MLA Handbook (7th Edition):

Gamble, Lena Jeanelle. “Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins.” 2010. Web. 23 Oct 2019.

Vancouver:

Gamble LJ. Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2010. [cited 2019 Oct 23]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1400.

Council of Science Editors:

Gamble LJ. Generation And Analysis Of The Oncolytic Efficacy Of A Conditionally Replicating Adenovirus Bearing Rgd Modifications On Pix And Fiber Capsid Proteins. [Doctoral Dissertation]. University of Alabama – Birmingham; 2010. Available from: http://contentdm.mhsl.uab.edu/u?/etd,1400

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