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Science 21 January 1994:
Vol. 263. no. 5145, pp. 375 - 377
DOI: 10.1126/science.8278810
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Articles

Science, Vol 263, Issue 5145, 375-377
Copyright © 1994 by American Association for the Advancement of Science

articles

Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor

B Lovejoy, A Cleasby, AM Hassell, K Longley, MA Luther, D Weigl, G McGeehan, AB McElroy, D Drewry, MH Lambert, and al. et

Glaxo Research Institute, Research Triangle Park, NC 27709.

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.


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