The open structure of a multi-drug-resistant HIV-1 protease is stabilized by crystal packing contacts.

ABSTRACT: The introduction of HIV-1 protease (HIV-PR) inhibitors has led to a dramatic increase in patient survival; however, these gains are threatened by the emergence of multi-drug-resistant strains. Design of inhibitors that overcome resistance would be greatly facilitated by deeper insight into the mechanistic events associated with binding of substrates and inhibitors, as well as an understanding of the effects of resistance mutations on the structure and dynamic behavior of HIV-PR. We previously reported a series of simulations that provide a model for HIV-PR dynamics, with spontaneous conversions between the bound and unbound crystal forms upon addition or removal of an inhibitor. Importantly, the unbound protease transiently sampled a third fully open state that permits entry to the active

SUBMITTER: Layten M 

PROVIDER: S-EPMC2532084 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature