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spinqualitylabelsall models PDB ID 1nhu Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.00Å
Ligands:
Activity:	RNA-directed RNA polymerase, with EC number 2.7.7.48
Coordinates:	save as pdb, mmCIF, xml

Hepatitis C virus RNA polymerase in complex with non-nucleoside analogue inhibitor

Overview

X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined to 2.0 and 2.9 A resolution. These noncompetitive inhibitors bind to the same site on the protein, approximately 35 A from the active site. The common features of binding include a large hydrophobic region and two hydrogen bonds between both oxygen atoms of a carboxylate group on the inhibitor and two main chain amide nitrogen atoms of Ser(476) and Tyr(477) on NS5B. The inhibitor-binding site lies at the base of the thumb domain, near its interface with the C-terminal extension of NS5B. The location of this inhibitor-binding site suggests that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase.

About this Structure

1NHU is a Single protein structure of sequence from Hepatitis c virus. Full crystallographic information is available from OCA.

Reference

Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibition., Wang M, Ng KK, Cherney MM, Chan L, Yannopoulos CG, Bedard J, Morin N, Nguyen-Ba N, Alaoui-Ismaili MH, Bethell RC, James MN, J Biol Chem. 2003 Mar 14;278(11):9489-95. Epub 2002 Dec 30. PMID:12509436

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