STRUCTURE OF THE CATALYTIC DOMAIN OF FIBROBLAST COLLAGENASE COMPLEXEDWITH AN INHIBITOR

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 be en associated with several pathologies. The 2.4 angstrom resolution st ructure of the inhibited enzyme revealed that, in addition to the cata lytic zinc, there is a second zinc ion and a calcium ion which play a major role in stabilizing the tertiary structure of collagenase. Despi te scant sequence homology, collagenase shares structural homology wit h two other endoproteinases, bacterial thermolysin and crayfish astaci n. 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.