2hd0

From Proteopedia

Structure of the catalytic domain of hepatitis C virus NS2

Overview

Hepatitis C virus is a major global health problem affecting an estimated, 170 million people worldwide. Chronic infection is common and can lead to, cirrhosis and liver cancer. There is no vaccine available and current, therapies have met with limited success. The viral RNA genome encodes a, polyprotein that includes two proteases essential for virus replication., The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the, polyprotein. NS3-4A is characterized as a serine protease with a, chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease, remains unresolved. Here we report the crystal structure of the catalytic, domain of the NS2-3 protease at 2.3 A resolution. The structure reveals a, dimeric cysteine protease with two composite active sites. For each active, site, the catalytic histidine and glutamate residues are contributed by, one monomer, and the nucleophilic cysteine by the other. The, carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation, of a composite active site occurs in the context of the viral polyprotein, expressed in mammalian cells. These features offer unexpected insights, into polyprotein processing by hepatitis C virus and new opportunities for, antiviral drug design.

About this Structure

2HD0 is a Single protein structure of sequence from Hepatitis c virus with DMU and BOG as ligands. Full crystallographic information is available from OCA.

Reference

Structure of the catalytic domain of the hepatitis C virus NS2-3 protease., Lorenz IC, Marcotrigiano J, Dentzer TG, Rice CM, Nature. 2006 Aug 17;442(7104):831-5. Epub 2006 Jul 23. PMID:16862121

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