NMR Studies of the Structure and Interactions of an HIV-Inhibitor Complex

Torchia, D A.

Abstract

The purpose of this project is to develop NMR methods to study the dynamics and structure of HIV and related proteins in the crystalline state and in solution. The purpose of this work is to obtain a better understanding of the structure-function relationship. In a specific application, we will determine the structure of an HIV protease-inhibitor complex. Our ultimate goal is to use the knowledge of structure to develop a rational design of inhibitors of the HIV protease.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Dental & Craniofacial Research (NIDCR)
• Type: Intramural Research (Z01)
• Project #: 1Z01DE000507-01
• Application #: 3875274
• Support Year: 1
• Fiscal Year: 1990

Institution

• Name: National Institute of Dental & Craniofacial Research
• Country: United States

Publications

Ishima, Rieko; Torchia, Dennis A (2006) Accuracy of optimized chemical-exchange parameters derived by fitting CPMG R2 dispersion profiles when R2(0a) not = R2(0b). J Biomol NMR 34:209-19

Ishima, Rieko; Torchia, Dennis A (2005) Error estimation and global fitting in transverse-relaxation dispersion experiments to determine chemical-exchange parameters. J Biomol NMR 32:41-54

Ishima, Rieko; Baber, James; Louis, John M et al. (2004) Carbonyl carbon transverse relaxation dispersion measurements and ms-micros timescale motion in a protein hydrogen bond network. J Biomol NMR 29:187-98

Jacob, Jaison; Louis, John M; Richter, B W M et al. (2004) The C-terminal domain of viral IAP associated factor (cVIAF) is a structural homologue of phosducin: resonance assignments and secondary structure of the C-terminal domain of VIAF. J Biomol NMR 28:197-8

Ishima, Rieko; Torchia, Dennis A (2003) Extending the range of amide proton relaxation dispersion experiments in proteins using a constant-time relaxation-compensated CPMG approach. J Biomol NMR 25:243-8

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

Freedberg, Daron I; Ishima, Rieko; Jacob, Jaison et al. (2002) Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations. Protein Sci 11:221-32

Korzhnev, Dmitry M; Skrynnikov, Nikolai R; Millet, Oscar et al. (2002) An NMR experiment for the accurate measurement of heteronuclear spin-lock relaxation rates. J Am Chem Soc 124:10743-53