HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir.

ABSTRACT: Hepatitis B virus (HBV) reverse transcriptase (RT) is essential for viral replication and is an important drug target. Nonetheless, the notorious insolubility of HBV RT has hindered experimental structural studies and structure-based drug design. Here, we demonstrate that a Q151M substitution alone at the nucleotide-binding site (N-site) of human immunodeficiency virus type-1 (HIV-1) RT renders HIV-1 highly sensitive to entecavir (ETV), a potent nucleoside analogue RT inhibitor (NRTI) against HBV. The results suggest that Met151 forms a transient hydrophobic interaction with the cyclopentyl methylene of ETV, a characteristic hydrophobic moiety of ETV. We thus solved the crystal structures of HIV-1 RT^Q151M:DNA complex with bound dGTP or ETV-triphosphate (ETV-TP). The structures r

SUBMITTER: Yasutake Y 

PROVIDER: S-EPMC5785976 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature