Publication Abstract from PubMed
Several crystal structures of the hepatitis C virus NS5B protein (genotype-1b, strain J4) complexed with metal ions, single-stranded RNA or nucleoside-triphosphates have been determined. These complexes illustrate how conserved amino acid side-chains, together with essential structural features within the active site, control nucleotide binding and likely mediate de-novo initiation. The incoming nucleotide interacts with several basic residues from an extension on the NS5B fingers domain, a beta-hairpin from the NS5B thumb domain and the C-terminal arm. The modular, bi-partite fingers domain carries a long binding groove which guides the template towards the catalytic site. The apo-polymerase structure provides unprecedented insights into potential non-nucleoside inhibitor binding sites located between palm and thumb near motif E, which is unique to RNA polymerases and reverse transcriptases.
Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation.,O'Farrell D, Trowbridge R, Rowlands D, Jager J J Mol Biol. 2003 Feb 28;326(4):1025-35. PMID:12589751[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
