Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d).
- 30 August 1994
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (18) , 8447-8451
- https://doi.org/10.1073/pnas.91.18.8447
Abstract
The structure of the metalloproteinase and hemorrhagic toxin atrolysin C form d (EC 3.4.24.42), from the venom of the western diamondback rattlesnake Crotalus atrox, has been determined to atomic resolution by x-ray crystallographic methods. This study illuminates the nature of inhibitor binding with natural (< Glu-Asn-Trp, where < Glu is pyroglutamic acid) and synthetic (SCH 47890) ligands. The primary specificity pocket is exceptionally deep; the nature of inhibitor and productive substrate binding is discussed. Insights gained from the study of these complexes facilitate the design of potential drugs to treat diseases where matrix metalloproteinases have been implicated, e.g., arthritis and tumor metastasis.Keywords
This publication has 39 references indexed in Scilit:
- On the size of the active site in proteases. I. PapainPublished by Elsevier ,2005
- Core tracing: depicting connections between features in electron densityActa Crystallographica Section D-Biological Crystallography, 1994
- Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc‐binding environments (HEXXHXXGXXH and Met‐turn) and topologies and should be grouped into a common family, the ‘metzincins’FEBS Letters, 1993
- A Secondary Structure Prediction of the Hemorrhagic Metalloprotease FamilyBiochemical and Biophysical Research Communications, 1993
- Refined 1·8 Å X-ray Crystal Structure of Astacin, a Zinc-endopeptidase from the Crayfish Astacus astacus L.: Structure Determination, Refinement, Molecular Structure and Comparison with ThermolysinJournal of Molecular Biology, 1993
- Human leukocyte and porcine pancreatic elastase: x-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitorsBiochemistry, 1989
- Partial purification and characterization of a neutral protease which cleaves type IV collagenBiochemistry, 1981
- Design of Specific Inhibitors of Angiotensin-Converting Enzyme: New Class of Orally Active Antihypertensive AgentsScience, 1977
- Animal collagenases: Specificity of action, and structures of the substrate cleavage siteBiochemical and Biophysical Research Communications, 1974
- Bradykinin-potentiating peptides from the venom of Agkistrodon halys. Isolation of five bradykinin potentiators and the amino acid sequences of two of them, potentiators B and CBiochemistry, 1971