Observation of a tetrahedral reaction intermediate in the HIV-1 protease-substrate complex.

ABSTRACT: HIV-1 protease is an effective target for the design of drugs against AIDS. To help this process of drug design, three-dimensional structures have been determined of complexes between HIV-1 protease and a variety of transition-state analogue inhibitors. The true transition state, however, has not been structurally characterized. The crystal structure of the C95M/C1095A HIV-1 protease tethered dimer shows a distinctive feature in which the two flaps of the enzyme are in a 'closed conformation' even in the unliganded state. This unique feature has been utilized here to study the structure of HIV-1 protease complexed to an oligopeptide substrate of amino acid sequence His-Lys-Ala-Arg-Val-Leu*NPhe-Glu-Ala-Nle-Ser (where * denotes the cleavage site, and NPhe and Nle denote p-nitrophenylalanine

SUBMITTER: Kumar M 

PROVIDER: S-EPMC1175113 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature