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You searched for +publisher:"Drexel University" +contributor:("Loll, Patrick J."). Showing records 1 – 3 of 3 total matches.

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Drexel University

1. Melideo, Scott L. Towards Understanding the Pathway for Hydrogen Sulfide Metabolism.

Degree: 2015, Drexel University

Hydrogen sulfide (H2S) is the most recently identified member of a small family of labile biological signaling molecules, termed gasotransmitters, which includes nitric oxide and carbon monoxide. H2S is the only gasotransmitter that is enzymatically metabolized a process that occurs in the mitochondria. H2S needs to be tightly regulated because it is toxic at high concentrations and leads to physiological defects at low concentrations. For example, a genetic defect that affects the metabolic pathway of H2S is ethylmalonic encephalopathy, a fatal disorder that is characterized by extremely high levels of H2S. On the other hand, animal model studies provide compelling evidence for a functional association between abnormally low levels of H2S and cardiovascular disease. In light of H2S’s critical role, the goal of this thesis was to identify and characterize two human enzymes that are proposed to comprise part of the metabolic pathway of H2S in mammals: Sulfide:quinone oxidoreductase (SQOR) and thiosulfate:glutathione sulfurtransferase (TST). The present study postulates that human sulfide:quinone oxidoreductase (SQOR), a membrane-bound enzyme, catalyzes the first step in the mitochondrial metabolism of H2S. The reaction involves a two-electron oxidation of H2S to S0 (sulfane sulfur) and uses coenzyme Q as an electron acceptor. The fact that SQOR is a membrane-associated protein has made its expression and isolation challenging. We successfully purified and characterized human SQOR. Cyanide, sulfite, or sulfide can act as the sulfane sulfur acceptor in reactions that produce thiocyanate, thiosulfate, or a putative sulfur analog of hydrogen peroxide (H2S2), respectively. Thiosulfate is a known intermediate in the oxidation of H2S within animals and the major product formed in glutathione-depleted cells or mitochondria. Importantly, oxidation of H2S by SQOR with sulfite as the sulfane sulfur acceptor is rapid and highly efficient at physiological pH (kcat/Km,H2S = 2.9 × 107 M-1 s-1). We propose that this highly efficient oxidation of H2S by SQOR is the predominant source of the thiosulfate in mammalian tissues and that sulfite is the physiological acceptor of the sulfane sulfur. Our proposal opposes an alternative hypothesis that glutathione is an acceptor of the sulfane sulfur, which we have compelling evidence against. The discovery that sulfite was the physiological acceptor of the sulfane sulfur and SQOR produced thiosulfate, led us to postulate a role in H2S metabolism for a TST that transfers the sulfane sulfur of thiosulfate to glutathione producing GSS- and sulfite. We postulate that the TST links together the SQOR and sulfur dioxygenase (SDO) steps in the pathway because it consumes the thiosulfate from the SQOR reaction and produces glutathione persulfide (GSS-), a substrate required for SDO. Although an active TST enzyme had been found in yeast, attempts by other laboratories to isolate and characterize the mammalian enzyme have been unsuccessful. We also discovered genes that encode for human and yeast TST… Advisors/Committee Members: Loll, Patrick J. (Patrick John), 1958-, College of Medicine.

Subjects/Keywords: Biochemistry; Biochemical Phenomena

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

APA (6th Edition):

Melideo, S. L. (2015). Towards Understanding the Pathway for Hydrogen Sulfide Metabolism. (Thesis). Drexel University. Retrieved from http://hdl.handle.net/1860/idea:7151

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

Chicago Manual of Style (16th Edition):

Melideo, Scott L. “Towards Understanding the Pathway for Hydrogen Sulfide Metabolism.” 2015. Thesis, Drexel University. Accessed August 25, 2019. http://hdl.handle.net/1860/idea:7151.

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

MLA Handbook (7th Edition):

Melideo, Scott L. “Towards Understanding the Pathway for Hydrogen Sulfide Metabolism.” 2015. Web. 25 Aug 2019.

Vancouver:

Melideo SL. Towards Understanding the Pathway for Hydrogen Sulfide Metabolism. [Internet] [Thesis]. Drexel University; 2015. [cited 2019 Aug 25]. Available from: http://hdl.handle.net/1860/idea:7151.

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

Council of Science Editors:

Melideo SL. Towards Understanding the Pathway for Hydrogen Sulfide Metabolism. [Thesis]. Drexel University; 2015. Available from: http://hdl.handle.net/1860/idea:7151

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


Drexel University

2. Rao, Maya V. Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease.

Degree: 2017, Drexel University

p97 is an essential ATPase associated with various cellular activities (AAA+) that functions as a segregase in diverse cellular processes, including the maintenance of proteostasis. p97 interacts with different cofactors that target it to distinct pathways; an important example is the deubiquitinase ataxin3, which collaborates with p97 in endoplasmic reticulum associated degradation. However, the molecular details of this interaction have been unclear. We have characterized the binding of ataxin3 to p97, showing that ataxin3 binds with low-micromolar affinity to both wild-type p97 and mutants linked to degenerative disorders known as multisystem proteinopathy 1 (MSP1); we further showed that the stoichiometry of binding is one ataxin3 molecule per p97 hexamer. We have mapped the binding determinants on each protein, demonstrating that ataxin3’s p97/VCP-binding motif (VBM) interacts with the inter-lobe cleft in the N-domain of p97. We also probed the nucleotide dependence of this interaction, confirming that ataxin3 and p97 associate in the presence of ATP and in the absence of nucleotide, but not in the presence of ADP. Our experiments suggest that an ADP-driven downward movement of the p97 N-terminal domain dislodges ataxin3 by inducing a steric clash between the D1-domain and ataxin3’s C-terminus. In contrast, MSP1 mutants of p97 bind ataxin3 irrespective of their nucleotide state, indicating a failure by these mutants to translate ADP binding into a movement of the N-terminal domain. Our model provides a mechanistic explanation for how nucleotides regulate the p97-ataxin3 interaction and why atypical cofactor binding is observed with MSP1 mutants.

Ph.D., Biochemistry  – Drexel University, 2017

Advisors/Committee Members: Loll, Patrick J. (Patrick John), 1958-, College of Medicine.

Subjects/Keywords: Biochemistry; Molecular biology; Adenosine triphosphatase; Enzymes; Protein-protein interactions

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

APA (6th Edition):

Rao, M. V. (2017). Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease. (Thesis). Drexel University. Retrieved from http://hdl.handle.net/1860/idea:7662

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

Chicago Manual of Style (16th Edition):

Rao, Maya V. “Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease.” 2017. Thesis, Drexel University. Accessed August 25, 2019. http://hdl.handle.net/1860/idea:7662.

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

MLA Handbook (7th Edition):

Rao, Maya V. “Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease.” 2017. Web. 25 Aug 2019.

Vancouver:

Rao MV. Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease. [Internet] [Thesis]. Drexel University; 2017. [cited 2019 Aug 25]. Available from: http://hdl.handle.net/1860/idea:7662.

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

Council of Science Editors:

Rao MV. Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease. [Thesis]. Drexel University; 2017. Available from: http://hdl.handle.net/1860/idea:7662

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


Drexel University

3. Fakhoury, Guila. Expression and Purification of The Hepatitis B Virus X Protein.

Degree: 2017, Drexel University

The hepatitis B virus (HBV) genome is made of a small partially double-stranded, circular DNA that encodes four open-reading frames. One important protein encoded by the smallest open reading frame of the viral genome is HBV protein X; this protein has been shown to be essential for HBV replication. It has also been shown that the X protein plays an important role in the development of HBV-associated HCC. To this date, there is no three-dimensional structure available for HBx, and this may be due to the presence of disordered regions in HBx. Understanding the structure of X is essential for understanding its ordered and disordered boundaries as well as when using in-vitro assays to understand HBx functions. We propose expressing different truncated version of protein X in bacterial system, using different vectors that help stabilize the protein during purification. We expressed eight different versions of protein X plus, including the full-length protein, in three different vectors using BL21 bacterial cells as hosts. Our goal was to test the expression of these versions of the protein using small test-expression to see if any of the regions of the protein can be expressed. We use the same conditions used on large-scale expression. Our results show low expression of three different constructs in one of the vectors used in this experiment. Conditions can be optimized to yield higher expression. Overall, we have promising results that if optimized could lead to a better expression and for the first time give us information about HBx three-dimensional structure.

M.S., Biomedical Studies  – Drexel University, 2017

Advisors/Committee Members: Loll, Patrick J. (Patrick John), 1958-, College of Medicine.

Subjects/Keywords: Biochemistry

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

APA (6th Edition):

Fakhoury, G. (2017). Expression and Purification of The Hepatitis B Virus X Protein. (Thesis). Drexel University. Retrieved from http://hdl.handle.net/1860/idea:7748

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

Chicago Manual of Style (16th Edition):

Fakhoury, Guila. “Expression and Purification of The Hepatitis B Virus X Protein.” 2017. Thesis, Drexel University. Accessed August 25, 2019. http://hdl.handle.net/1860/idea:7748.

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

MLA Handbook (7th Edition):

Fakhoury, Guila. “Expression and Purification of The Hepatitis B Virus X Protein.” 2017. Web. 25 Aug 2019.

Vancouver:

Fakhoury G. Expression and Purification of The Hepatitis B Virus X Protein. [Internet] [Thesis]. Drexel University; 2017. [cited 2019 Aug 25]. Available from: http://hdl.handle.net/1860/idea:7748.

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

Council of Science Editors:

Fakhoury G. Expression and Purification of The Hepatitis B Virus X Protein. [Thesis]. Drexel University; 2017. Available from: http://hdl.handle.net/1860/idea:7748

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

.