The proposal's short-term aim is to eludicate the molecular basis for the action of resistant variants of Human Immunodeficiency Virus 1 (HIV-1) protease by comparing the structures and activities of selected mutants of HIV-1 and Rous sarcoma virus proteases. The specificity studies proposed will be: 1) to cover a broader set of oligopeptide substrates in order to more fully characterize the inhibitor-resistant HIV-1 protease mutants; and 2) promote new studies on the molecular basis for the specificity of the related human T-cell leukemia virus type 1 (HTLV-1) protease. The long-term aim is to predict new protease inhibitors and therapeutic strategies to overcome the problem of drug-resistance.
| Kadas, Janos; Boross, Peter; Weber, Irene T et al. (2008) C-terminal residues of mature human T-lymphotropic virus type 1 protease are critical for dimerization and catalytic activity. Biochem J 416:357-64 |
| Eizert, Helga; Bander, Palma; Bagossi, Peter et al. (2008) Amino acid preferences of retroviral proteases for amino-terminal positions in a type 1 cleavage site. J Virol 82:10111-7 |
| Louis, John M; Ishima, Rieko; Torchia, Dennis A et al. (2007) HIV-1 protease: structure, dynamics, and inhibition. Adv Pharmacol 55:261-98 |
| Kovalevsky, Andrey Y; Liu, Fengling; Leshchenko, Sofiya et al. (2006) Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114. J Mol Biol 363:161-73 |
| Liu, Fengling; Boross, Peter I; Wang, Yuan-Fang et al. (2005) Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. J Mol Biol 354:789-800 |
