1k2i

Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin

spinqualitylabelsall models 1k2i, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1k2i is a 1 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SN1, SO4 Related: 1gct Activity: Chymotrypsin, with EC number 3.4.21.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to chymotrypsin reveals that this inhibitor forms a planar cinnamate acyl-enzyme complex. The phenyl ring of the bound inhibitor forms numerous van der Waals contacts in the S1 pocket of the enzyme, with the p-hydroxyl group donating a hydrogen bond to the main-chain oxygen atom of Ser217, and the o-hydroxyl group forming a water-mediated hydrogen bond with the carbonyl oxygen of Val227. The structure of the acyl-enzyme complex suggests that the mechanism of inhibition of 7-HC involves nucleophilic attack by the Ser195 O(gamma) atom on the carbonyl carbon atom of the inhibitor, accompanied by the breaking of the 2-pyrone ring of the inhibitor, and leading to the formation of a cinnamate acyl-enzyme derivative via a tetrahedral transition state. Comparisons with structures of photoreversible cinnamates bound to chymotrypsin reveal that although 7-HC interacts with the enzyme in a similar fashion, the binding of 7-HC to chymotrypsin takes place in a productive conformation in contrast to the photoreversible cinnamates. In summary, the 7-HC-chymotrypsin complex provides basic insight into the inhibition of chymotrypsin by natural coumarins and provides a structural basis for the design of more potent mechanism-based inhibitors against a wide range of biologically important chymotrypsin-like enzymes. Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin.,Ghani U, Ng KK, Atta-ur-Rahman, Choudhary MI, Ullah N, James MN J Mol Biol. 2001 Nov 30;314(3):519-25. PMID:11846564 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Chymotrypsin 3D structures

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