Work has been carried out on a number of structural problems related to proteins derived from the HIV-1 virus. We produced and characterized a mutant protease can exist as a metastable monomer.We applied novel methodological approaches and media to measure residual dipolar couplings.The folding and thermodynamics of the potent HIV-inactivating molecule cyanovirin-N was studied and mutants thereof were structurally characterized. In addition, binding to high mannose carbohydrates was structurally and energetically characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK029022-14
Application #
6673407
Study Section
(LCP)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Barrientos, Laura G; Gronenborn, Angela M (2005) The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy. Mini Rev Med Chem 5:21-31
Ding, Keyang; Gronenborn, Angela M (2004) Sensitivity-enhanced IPAP experiments for measuring one-bond 13C'-13Calpha and 13Calpha-1Halpha residual dipolar couplings in proteins. J Magn Reson 167:253-8
Barrientos, Laura G; Lasala, Fatima; Delgado, Rafael et al. (2004) Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity. Structure 12:1799-807
Ding, Keyang; Gronenborn, Angela M (2004) Protein Backbone 1H(N)-13Calpha and 15N-13Calpha residual dipolar and J couplings: new constraints for NMR structure determination. J Am Chem Soc 126:6232-3
Ishima, Rieko; Torchia, Dennis A; Lynch, Shannon M et al. (2003) Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor. J Biol Chem 278:43311-9
Louis, John M; Ishima, Rieko; Nesheiwat, Issa et al. (2003) Revisiting monomeric HIV-1 protease. Characterization and redesign for improved properties. J Biol Chem 278:6085-92
Katoh, Etsuko; Louis, John M; Yamazaki, Toshimasa et al. (2003) A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex. Protein Sci 12:1376-85
Barrientos, Laura G; Louis, John M; Ratner, Daniel M et al. (2003) Solution structure of a circular-permuted variant of the potent HIV-inactivating protein cyanovirin-N: structural basis for protein stability and oligosaccharide interaction. J Mol Biol 325:211-23
Ding, Keyang; Gronenborn, Angela M (2003) Sensitivity-enhanced 2D IPAP, TROSY-anti-TROSY, and E.COSY experiments: alternatives for measuring dipolar 15N-1HN couplings. J Magn Reson 163:208-14
Barrientos, Laura G; O'Keefe, Barry R; Bray, Mike et al. (2003) Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res 58:47-56

Showing the most recent 10 out of 23 publications