Structural Interaction of Natural and Synthetic Inhibitors with the Venom Metalloproteinase, Atrolysin C (Ht-d)

*Biographics Laboratory, Dept. of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843;

+Max-Planck Institute of Biochemistry, D-82152 Martinsried, Germany;

^Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033;

**Biomolecular Research Facility, University of Virginia Health Sciences Center, Charlottesville, VA 22908

Communicated to Proc. Natl. Acad. Sci. USA by Sir Derek H. R. Barton, FRS

The structure of the native and inhibited metalloproteinase and haemorrhagic toxin, atrolysin C (Ht-d), from the venom of the western diamondback rattlesnake, Crotalus atrox, has been obtained to atomic resolution by X-ray crystallographic methods. This study illuminates the nature of inhibitor binding with natural (pENW) and synthetic (SCH) ligands. The primary specificity pocket is found to be exceptionally deep; the nature of inhibitor and productive substrate binding is discussed. Insights gained from the study of theses complexes facilitate the design of potential drugs to treat diseases where MMPs have been emplicated, e.g., arthritis and tumor metastasis.

"Structural Interaction of Natural and Synthetic Inhibitors with the Venom Metalloproteinase, Atrolysin C (Ht-d)", D.Zhang, I.Botos, F.X.Gomis-Ruth, R.Doll, C.Blood, F.G.Njoroge, J. Fox, W.Bode & E.F.Meyer, Proc. Natl. Acad. Sci. USA(1994) 91:8447-8451.

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