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

共 79 条

[11] AT LEAST 12 GENOTYPES OF HEPATITIS-C VIRUS PREDICTED BY SEQUENCE-ANALYSIS OF THE PUTATIVE E1-GENE OF ISOLATES COLLECTED WORLDWIDE
BUKH, J
PURCELL, RH
MILLER, RH
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) : 8234 - 8238
[12] BURLEY SK, 1988, ADV PROTEIN CHEM, V39, P125
[13] RIBBONS 2 0
CARSON, M
[J]. JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1991, 24 : 958 - &
[14] MUTAGENESIS OF THE YELLOW-FEVER VIRUS NS2B PROTEIN - EFFECTS ON PROTEOLYTIC PROCESSING, NS2B-NS3 COMPLEX-FORMATION, AND VIRAL REPLICATION
CHAMBERS, TJ
NESTOROWICZ, A
AMBERG, SM
RICE, CM
[J]. JOURNAL OF VIROLOGY, 1993, 67 (11) : 6797 - 6807
[15] MUTAGENESIS OF THE YELLOW-FEVER VIRUS NS2B/3 CLEAVAGE SITE - DETERMINANTS OF CLEAVAGE SITE-SPECIFICITY AND EFFECTS ON POLYPROTEIN PROCESSING AND VIRAL REPLICATION
CHAMBERS, TJ
NESTOROWICZ, A
RICE, CM
[J]. JOURNAL OF VIROLOGY, 1995, 69 (03) : 1600 - 1605
[16] EVIDENCE THAT THE N-TERMINAL DOMAIN OF NONSTRUCTURAL PROTEIN NS3 FROM YELLOW-FEVER VIRUS IS A SERINE PROTEASE RESPONSIBLE FOR SITE-SPECIFIC CLEAVAGES IN THE VIRAL POLYPROTEIN
CHAMBERS, TJ
WEIR, RC
GRAKOUI, A
MCCOURT, DW
BAZAN, JF
FLETTERICK, RJ
RICE, CM
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (22) : 8898 - 8902
[17] YELLOW-FEVER VIRUS PROTEIN-NS2A, PROTEIN-NS2B, AND PROTEIN-NS4B - IDENTIFICATION AND PARTIAL N-TERMINAL AMINO-ACID SEQUENCE-ANALYSIS
CHAMBERS, TJ
MCCOURT, DW
RICE, CM
[J]. VIROLOGY, 1989, 169 (01) : 100 - 109
[18] ISOLATION OF A CDNA CLONE DERIVED FROM A BLOOD-BORNE NON-A, NON-B VIRAL-HEPATITIS GENOME
CHOO, QL
KUO, G
WEINER, AJ
OVERBY, LR
BRADLEY, DW
HOUGHTON, M
[J]. SCIENCE, 1989, 244 (4902) : 359 - 362
[19] GENETIC ORGANIZATION AND DIVERSITY OF THE HEPATITIS-C VIRUS
CHOO, QL
RICHMAN, KH
HAN, JH
BERGER, K
LEE, C
DONG, C
GALLEGOS, C
COIT, D
MEDINASELBY, A
BARR, PJ
WEINER, AJ
BRADLEY, DW
KUO, G
HOUGHTON, M
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) : 2451 - 2455
[20] Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor
Ding, JZ
McGrath, WJ
Sweet, RM
Mangel, WF
[J]. EMBO JOURNAL, 1996, 15 (08) : 1778 - 1783

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