Ontology highlight
ABSTRACT:
SUBMITTER: Kovalevsky AY
PROVIDER: S-EPMC1781337 | biostudies-literature | 2006 Oct
REPOSITORIES: biostudies-literature
Kovalevsky Andrey Y AY Liu Fengling F Leshchenko Sofiya S Ghosh Arun K AK Louis John M JM Harrison Robert W RW Weber Irene T IT
Journal of molecular biology 20060804 1
TMC114 (darunavir) is a promising clinical inhibitor of HIV-1 protease (PR) for treatment of drug resistant HIV/AIDS. We report the ultra-high 0.84 A resolution crystal structure of the TMC114 complex with PR containing the drug-resistant mutation V32I (PR(V32I)), and the 1.22 A resolution structure of a complex with PR(M46L). These structures show TMC114 bound at two distinct sites, one in the active-site cavity and the second on the surface of one of the flexible flaps in the PR dimer. Remarka ...[more]