Flap-site Fragment Restores Back Wild-type Behaviour in Resistant Form of HIV Protease.

ABSTRACT: HIV-1 protease (HIV-PR) performs a vital step in the virus life cycle which makes it an excellent target for drug therapy. However, due to the error-prone of HIV reverse transcriptase, mutations in HIV-PR often occur, inducing drug-resistance to inhibitors. Some HIV-PR mutations can make the flaps of the enzyme more flexible thus increasing the flaps opening rate and inhibitor releasing. It has been shown that by targeting novel binding sites on HIV-PR with small molecules, it is possible to alter the equilibrium of flap conformational states. A previous fragment-based crystallographic screen have found two novel binding sites for small fragments in the inhibited, closed form of HIV-PR, termed flap and exo sites. While these experiments were performed in wild type HIV-PR, it still remains

SUBMITTER: Luchi A 

PROVIDER: S-EPMC6501176 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature