Predicted structure of the hepatitis B virus polymerase reveals an ancient conserved protein fold.

ABSTRACT: Hepatitis B virus (HBV) chronically infects >250 million people. It replicates by a unique protein-primed reverse transcription mechanism, and the primary anti-HBV drugs are nucleos(t)ide analogs targeting the viral polymerase (P). P has four domains compared to only two in most reverse transcriptases: the terminal protein (TP) that primes DNA synthesis, a spacer, the reverse transcriptase (RT), and the ribonuclease H (RNase H). Despite being a major drug target and catalyzing a reverse transcription pathway very different from the retroviruses, HBV P has resisted structural analysis for decades. Here, we exploited computational advances to model P. The TP wrapped around the RT domain rather than forming the anticipated globular domain, with the priming tyrosine poised over the RT active s

SUBMITTER: Tajwar R 

PROVIDER: S-EPMC9601786 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature