|
|
| Line 1: |
Line 1: |
| [[Image:1k2i.jpg|left|200px]] | | {{Seed}} |
| | [[Image:1k2i.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_1k2i| PDB=1k2i | SCENE= }} | | {{STRUCTURE_1k2i| PDB=1k2i | SCENE= }} |
|
| |
|
| '''Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin'''
| | ===Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_11846564}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11846564 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_11846564}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 30: |
Line 34: |
| [[Category: Ullah, N.]] | | [[Category: Ullah, N.]] |
| [[Category: Enzyme-inhibitor complex]] | | [[Category: Enzyme-inhibitor complex]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:13:18 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 21:32:16 2008'' |
