Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor.
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- CitationCopy to clipboard
Lovejoy B, Cleasby A, Hassell AM, Longley K, Luther MA, Weigl D, McGeehan G, McElroy AB, Drewry D, Lambert MH, et al.
Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor.
Science. 1994 Jan 21;263(5145):375-7.
- PubMed ID
- 8278810 [ View in PubMed]
- Abstract
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.