Structural Studies of AIDS Proteins by NMR

Gronenborn, Angela M.

Abstract

Work has been carried out on a number of structural problems related to proteins derived from the HIV-1 virus. The three dimensional solution structure of the complete ectodomain of SIV gp41 was determined and refined. In addition, the structure of a variant of the HIV-1 integrase N-terminal domain complexed with Cd instead of the naturally occuring Zn was solved. Based on the NMR structure of cyanovirin-N, the X- ray structure of this protein was solved. In addition, novel methodological approaches for improving the accuracy of NMR structures using residual dipolar couplings were developed and applied to a variety of systems. - Integrase, gp41, cyanovirin-N, NMR structures.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK029022-11
• Application #: 6289750
• Study Section: Special Emphasis Panel (LCP)
• Support Year: 11
• Fiscal Year: 1999

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases
• Country: United States

Publications

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