Proceedings of the National Academy of Sciences · 1994 · 136 citations · 38 references
Life SciencesMolecular BiologyPharmacologyDrug DesignDrug DiscoveryStructural BiologyEnzyme InhibitionLigand BindingProtein StructureProtein-ligand BindingProtein-ligand InteractionsProtein-ligand RecognitionMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesProtease InhibitorsSnake Venom MetalloproteinasesStructural InteractionSubstrate Binding PocketsSubstrate Binding SpecificityToxin Structure
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.
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Crystallographic <i>R</i> Factor Refinement by Molecular Dynamics
Axel T. Brünger, John Kuriyan, Martin Karplus · Science · 1987 · 2K citations
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