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 proteins and related proteins in solution in order obtain a better understanding of their structure-function relationships. 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 #: 1Z01DE000507-02
• Application #: 3854242
• Support Year: 2
• Fiscal Year: 1991

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