1k2i
From Proteopedia
(New page: 200px<br /><applet load="1k2i" size="450" color="white" frame="true" align="right" spinBox="true" caption="1k2i, resolution 1.8Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1k2i.jpg|left|200px]]<br /><applet load="1k2i" size=" | + | [[Image:1k2i.jpg|left|200px]]<br /><applet load="1k2i" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1k2i, resolution 1.8Å" /> | caption="1k2i, resolution 1.8Å" /> | ||
'''Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin'''<br /> | '''Crystal Structure of Gamma-Chymotrypsin in Complex with 7-Hydroxycoumarin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 1.8 A crystal structure of 7-hydroxycoumarin (7-HC) bound to | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1K2I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with SO4 and SN1 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chymotrypsin Chymotrypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.1 3.4.21.1] Full crystallographic information is available from [http:// | + | 1K2I is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=SN1:'>SN1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Chymotrypsin Chymotrypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.1 3.4.21.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K2I OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Atta-ur-Rahman]] | [[Category: Atta-ur-Rahman]] | ||
| - | [[Category: Choudhary, M | + | [[Category: Choudhary, M I.]] |
[[Category: Ghani, U.]] | [[Category: Ghani, U.]] | ||
| - | [[Category: James, M | + | [[Category: James, M N.G.]] |
| - | [[Category: Ng, K | + | [[Category: Ng, K K.S.]] |
[[Category: Ullah, N.]] | [[Category: Ullah, N.]] | ||
[[Category: SN1]] | [[Category: SN1]] | ||
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[[Category: enzyme-inhibitor complex]] | [[Category: enzyme-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:29:28 2008'' |
Revision as of 11:29, 21 February 2008
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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.
About this Structure
1K2I is a Single protein structure of sequence from Bos taurus with and as ligands. Active as Chymotrypsin, with EC number 3.4.21.1 Full crystallographic information is available from OCA.
Reference
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
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