STRUCTURE OF THE CATALYTIC DOMAIN OF FIBROBLAST COLLAGENASE COMPLEXED WITH AN INHIBITOR

被引：316

作者：

LOVEJOY, B ^{[1
]}

CLEASBY, A ^{[1
]}

HASSELL, AM ^{[1
]}

LONGLEY, K ^{[1
]}

LUTHER, MA ^{[1
]}

WEIGL, D ^{[1
]}

MCGEEHAN, G ^{[1
]}

MCELROY, AB ^{[1
]}

DREWRY, D ^{[1
]}

LAMBERT, MH ^{[1
]}

JORDAN, SR ^{[1
]}

机构：

[1] GLAXO GRP RES LTD,GREENFORD UB0 6HE,MIDDX,ENGLAND

来源：

SCIENCE | 1994年 / 263卷 / 5145期

关键词：

D O I：

10.1126/science.8278810

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Collagenase is a zinc-dependent endoproteinase and is a member of the matrix metalloproteinase (MMP) family of enzymes. The MMPs participate in connective tissue remodeling events and aberrant regulation has been associated with several pathologies. The 2.4 angstrom resolution structure of the inhibited enzyme revealed that, in addition to the catalytic zinc, there is a second zinc ion and a calcium ion which play a major role in stabilizing the tertiary structure of collagenase. Despite scant sequence homology, collagenase shares structural homology with two other endoproteinases, bacterial thermolysin and crayfish astacin. The detailed description of protein-inhibitor interactions present in the structure will aid in the design of compounds that selectively inhibit individual members of the MMP family. Such inhibitors will be useful in examining the function of MMPs in pathological processes.

引用

页码：375 / 377

页数：3

共 24 条

[1]

ALLAN JA, 1991, J CELL SCI, V99, P789

[2]

BECHERER JD, 1991, J CELL BIOCH G S, V15

[3] MATRIX METALLOPROTEINASES - A REVIEW [J].

BIRKEDALHANSEN, H ;

MOORE, WGI ;

BODDEN, MK ;

WINDSOR, LJ ;

BIRKEDALHANSEN, B ;

DECARLO, A ;

ENGLER, JA .

CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE, 1993, 4 (02) :197-250

[4] STRUCTURE OF ASTACIN AND IMPLICATIONS FOR ACTIVATION OF ASTACINS AND ZINC-LIGATION OF COLLAGENASES [J].

BODE, W ;

GOMISRUTH, FX ;

HUBER, R ;

ZWILLING, R ;

STOCKER, W .

NATURE, 1992, 358 (6382) :164-167

[5]

BROWN FK, IN PRESS J MED CHEM

[6] CRYSTALLOGRAPHIC R-FACTOR REFINEMENT BY MOLECULAR-DYNAMICS [J].

BRUNGER, AT ;

KURIYAN, J ;

KARPLUS, M .

SCIENCE, 1987, 235 (4787) :458-460

[7]

FUREY W, 1990, AM CRYSTALLOGR ASS 2, V18, P73

[8]

GOLDBERG GI, 1986, J BIOL CHEM, V261, P6600

[9] REFINED 1.8 ANGSTROM X-RAY CRYSTAL-STRUCTURE OF ASTACIN, A ZINC-ENDOPEPTIDASE FROM THE CRAYFISH ASTACUS-ASTACUS L - STRUCTURE DETERMINATION, REFINEMENT, MOLECULAR-STRUCTURE AND COMPARISON WITH THERMOLYSIN [J].

GOMISRUTH, FX ;

STOCKER, W ;

HUBER, R ;

ZWILLING, R ;

BODE, W .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 229 (04) :945-968

[10]

HASSELL AM, IN PRESS J MOL BIOL

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