Thesis Title: Solution NMR studies of HIV-1 reverse transcriptase
Graduation Date: Nov 21, 2016
Naima used solution NMR as a method to study protein structure and dynamics. Standard NMR experiments use protein uniformly labeled with NMR active nuclei, such as 15N, 13C and 2H. Each nucleus reports on its surrounding environment and the ability to obtain structural information depends on being able to resolve, and unambiguously assign all resonance frequencies to unique nuclei. However, for large proteins (> 30 kDa) resonance overlap properties render this process difficult. Naima's goal was to help develop NMR methods to study large proteins in solution. Towards this goal, she applied selective labeling methods to study the structure and dynamics of the 118 kDa HIV-1 reverse transcriptase, a major drug target in the treatment of HIV-1 infection. The NMR spectra of RT produced by these labeling methods contain less resonance overlap since only a few residues are labeled.
Chemistry (biochemistry track) University of North Carolina at Chapel Hill
PhD Advisor: Dr Angela Gronenborn
Current Location: Postdoctoral associate in the Rees lab at CalTech / HHMI.
- Sharaf, N. G.; Barnes, C. O.; Charlton, L. M.; Young, G. B.; Pielak, G. J., A bioreactor for in-cell protein NMR. J. Magn. Reson., 202 (2010) 140-146.
- Miklos AC, Li C, Sharaf NG, Pielak GJ. 2010. Volume exclusion and soft interaction effects on protein stability under crowded conditions. Biochemistry 49: 6984-6991.
- Sharaf NG, Poliner E, Slack RL, Christen MT, Byeon IJ, Parniak MA, Gronenborn AM, Ishima R. The p66 immature precursor of HIV-1 reverse transcriptase. Proteins. 2014; 82(10):2343-52
- Sharaf, N. G., and Gronenborn, A. M. 19F-Modified Proteins and 19F-Containing Ligands as Tools in Solution NMR Studies of Protein Interactions. Methods in Enzymology 2015; 565:67-95
- Sharaf NG, Ishima R, Gronenborn AM. Conformational Plasticity of the NNRTI-Binding Pocket in HIV-1 Reverse Transcriptase: A Fluorine Nuclear Magnetic Resonance Study. Biochemistry. 2016 Jul 19;55(28):3864-73>
- Sharaf NG, Brereton AE, Byeon IL, Andrew Karplus P, Gronenborn AM. NMR structure of the HIV-1 reverse transcriptase thumb subdomain. J Biomol NMR. 2016 66(4):273-280
- Sharaf NG, Xi Z, Ishima R, Gronenborn AM. The HIV-1 p66 homodimeric RT exhibits different conformations in the binding-competent and -incompetent NNRTI site. Proteins. 2017 doi: 10.1002/prot.25383 (in press)
Inventor in a provisional patent titled: Device for particulate NMR samples in a fluid.