STRUCTURAL INTERACTION OF NATURAL AND SYNTHETIC INHIBITORS WITH THE VENOM METALLOPROTEINASE, ATROLYSIN-C (FORM-D)

The structure of the metalloproteinase and hemorrhagic toxin atrolysin C form d (EC 3.4.24.42), from the venom of the western diamondback ra ttlesnake Crotalus atrox, has been determined to atomic resolution by x-ray crystallographic methods. This study illuminates the nature of i nhibitor binding with natural (<Glu-Asn-Trp, where <Glu is pyroglutami c acid) and synthetic (SCH 47890) ligands. The primary specificity poc ket is exceptionally deep; the nature of inhibitor and productive subs trate binding is discussed. Insights gained from the study of these co mplexes facilitate the design of potential drugs to treat diseases whe re matrix metalloproteinases have been implicated, e.g., arthritis and tumor metastasis.