Sharaf, Naima
(2017)
Solution NMR studies of HIV-1 reverse transcriptase.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
The human immunodeficiency virus (HIV-1) is a well-recognized threat to global public health,
with current estimates of ~37 million infected individuals worldwide [1]. While efforts to
develop an effective vaccine to prevent infection have not come to fruition, several FDA
approved drugs targeting HIV-1 have proven effective in reducing viral replication and
improving quality of life [2]. Yet, due to the increasing emergence of drug resistant variants, new
HIV-1 treatments are needed as the virus continues to evolve. Structure-based drug design is a
powerful approach for facilitating the development of new HIV-1 inhibitors [3], driven mainly
by x-ray crystallographic studies of viral proteins [4]. However, the static nature of
crystallographic studies necessitate complementary structural and dynamic studies to genuinely
understand protein-ligand interactions. In this thesis, solution NMR is used to investigate HIV-1
RT, a major therapeutic target in the fight against HIV-1 infection. HIV-1 reverse transcriptase
produces viral DNA from genomic RNA and is essential for the viral lifecycle [5]. Although the
structure of the mature heterodimer has been well characterized, less is known about RT
maturation from its p66 immature precursor, which so far has resisted crystallization. I used
NMR to investigate RT maturation and to elucidate RT interactions with FDA approved
inhibitors. Together the results of my thesis contribute to arrive at a more comprehensive
understanding of RT maturation and RT-inhibitor interactions.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Gronenborn, Angela | | | | | Committee Member | van der Wel, Patrick | | | | | Committee Member | Ishima, Rieko | | | | | Committee Member | Montelaro, Ronald | | | |
|
| Date: |
6 January 2017 |
| Date Type: |
Publication |
| Defense Date: |
21 November 2016 |
| Approval Date: |
6 January 2017 |
| Submission Date: |
9 December 2016 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
107 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Biophysics and Structural Biology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Fluorine NMR, HIV-1 reverse transcriptase |
| Date Deposited: |
06 Jan 2017 15:57 |
| Last Modified: |
07 Jan 2017 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/30651 |
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Solution NMR studies of HIV-1 reverse transcriptase. (deposited 06 Jan 2017 15:57)
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