Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide

被引：628

作者：

Kim, JL ^{[1
]}

Morgenstern, KA ^{[1
]}

Lin, C ^{[1
]}

Fox, T ^{[1
]}

Dwyer, MD ^{[1
]}

Landro, JA ^{[1
]}

Chambers, SP ^{[1
]}

Markland, W ^{[1
]}

Lepre, CA ^{[1
]}

OMalley, ET ^{[1
]}

Harbeson, SL ^{[1
]}

Rice, CM ^{[1
]}

Murcko, MA ^{[1
]}

Caron, PR ^{[1
]}

Thomson, JA ^{[1
]}

机构：

[1] WASHINGTON UNIV, SCH MED, DEPT MOL MICROBIOL, ST LOUIS, MO 63110 USA

来源：

CELL | 1996年 / 87卷 / 02期

关键词：

D O I：

10.1016/S0092-8674(00)81351-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An estimated 1% of the global human population is infected by hepatitis C viruses (HCVs), and there are no broadly effective treatments for the debilitating progression of chronic hepatitis C. A serine protease located within the HCV NS3 protein processes the viral polyprotein at four specific sites and is considered essential for replication. Thus, it emerges as an attractive target for drug design. We report here the 2.5 Angstrom resolution X-ray crystal structure of the NS3 protease domain complexed with a synthetic NS4A activator peptide. The protease has a chymotrypsin-like fold and features a tetrahedrally coordinated metal ion distal to the active site. The NS4A peptide intercalates within a beta sheet of the enzyme core.

引用

页码：343 / 355

页数：13

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