Transition states of native and drug-resistant HIV-1 protease are the same.

ABSTRACT: HIV-1 protease is an important target for the treatment of HIV/AIDS. However, drug resistance is a persistent problem and new inhibitors are needed. An approach toward understanding enzyme chemistry, the basis of drug resistance, and the design of powerful inhibitors is to establish the structure of enzymatic transition states. Enzymatic transition structures can be established by matching experimental kinetic isotope effects (KIEs) with theoretical predictions. However, the HIV-1 protease transition state has not been previously resolved using these methods. We have measured primary (14)C and (15)N KIEs and secondary (3)H and (18)O KIEs for native and multidrug-resistant HIV-1 protease (I84V). We observed (14)C KIEs ((14)V/K) of 1.029 ± 0.003 and 1.025 ± 0.005, (15)N KIEs ((15)V/K) of 0.9

SUBMITTER: Kipp DR 

PROVIDER: S-EPMC3340095 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature