1K2I
Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin
Summary for 1K2I
| Entry DOI | 10.2210/pdb1k2i/pdb |
| Related | 1GCT |
| Descriptor | CHYMOTRYPSINOGEN A, SULFATE ION, 2,4-DIHYDROXY-TRANS CINNAMIC ACID, ... (4 entities in total) |
| Functional Keywords | enzyme-inhibitor complex, hydrolase |
| Biological source | Bos taurus (cattle) |
| Cellular location | Secreted, extracellular space: P00766 |
| Total number of polymer chains | 1 |
| Total formula weight | 25962.26 |
| Authors | Ghani, U.,Ng, K.K.S.,Atta-ur-Rahman,Choudhary, M.I.,Ullah, N.,James, M.N.G. (deposition date: 2001-09-27, release date: 2001-12-05, Last modification date: 2024-12-25) |
| Primary citation | Ghani, U.,Ng, K.K.,Atta-ur-Rahman,Choudhary, M.I.,Ullah, N.,James, M.N. Crystal structure of gamma-chymotrypsin in complex with 7-hydroxycoumarin. J.Mol.Biol., 314:519-525, 2001 Cited by PubMed Abstract: 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. PubMed: 11846564DOI: 10.1006/jmbi.2001.5148 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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