1r9o
From Proteopedia
(New page: 200px<br /> <applet load="1r9o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r9o, resolution 2.0Å" /> '''Crystal Structure of...) |
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| - | [[Image:1r9o.gif|left|200px]]<br /> | + | [[Image:1r9o.gif|left|200px]]<br /><applet load="1r9o" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1r9o" size=" | + | |
caption="1r9o, resolution 2.0Å" /> | caption="1r9o, resolution 2.0Å" /> | ||
'''Crystal Structure of P4502C9 with Flurbiprofen bound'''<br /> | '''Crystal Structure of P4502C9 with Flurbiprofen bound'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of human P450 2C9 complexed with flurbiprofen was determined | + | The structure of human P450 2C9 complexed with flurbiprofen was determined to 2.0 A by x-ray crystallography. In contrast to other structurally characterized P450 2C enzymes, 2C5, 2C8, and a 2C9 chimera, the native catalytic domain of P450 2C9 differs significantly in the conformation of the helix F to helix G region and exhibits an extra turn at the N terminus of helix A. In addition, a distinct conformation of the helix B to helix C region allows Arg-108 to hydrogen bond with Asp-293 and Asn-289 on helix I and to interact directly with the carboxylate of flurbiprofen. These interactions position the substrate for regioselective oxidation in a relatively large active site cavity and are likely to account for the high catalytic efficiency exhibited by P450 2C9 for the regioselective oxidation of several anionic non-steroidal anti-inflammatory drugs. The structure provides a basis for interpretation of a number of observations regarding the substrate selectivity of P450 2C9 and the observed effects of mutations on catalysis. |
==About this Structure== | ==About this Structure== | ||
| - | 1R9O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEM, FLP and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] Full crystallographic information is available from [http:// | + | 1R9O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=FLP:'>FLP</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R9O OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Unspecific monooxygenase]] | [[Category: Unspecific monooxygenase]] | ||
| - | [[Category: Griffin, K | + | [[Category: Griffin, K J.]] |
| - | [[Category: Johnson, E | + | [[Category: Johnson, E F.]] |
| - | [[Category: Schoch, G | + | [[Category: Schoch, G A.]] |
| - | [[Category: Stout, C | + | [[Category: Stout, C D.]] |
| - | [[Category: Wester, M | + | [[Category: Wester, M R.]] |
| - | [[Category: Yano, J | + | [[Category: Yano, J K.]] |
[[Category: FLP]] | [[Category: FLP]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: p450]] | [[Category: p450]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:48:33 2008'' |
Revision as of 12:48, 21 February 2008
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Crystal Structure of P4502C9 with Flurbiprofen bound
Overview
The structure of human P450 2C9 complexed with flurbiprofen was determined to 2.0 A by x-ray crystallography. In contrast to other structurally characterized P450 2C enzymes, 2C5, 2C8, and a 2C9 chimera, the native catalytic domain of P450 2C9 differs significantly in the conformation of the helix F to helix G region and exhibits an extra turn at the N terminus of helix A. In addition, a distinct conformation of the helix B to helix C region allows Arg-108 to hydrogen bond with Asp-293 and Asn-289 on helix I and to interact directly with the carboxylate of flurbiprofen. These interactions position the substrate for regioselective oxidation in a relatively large active site cavity and are likely to account for the high catalytic efficiency exhibited by P450 2C9 for the regioselective oxidation of several anionic non-steroidal anti-inflammatory drugs. The structure provides a basis for interpretation of a number of observations regarding the substrate selectivity of P450 2C9 and the observed effects of mutations on catalysis.
About this Structure
1R9O is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Unspecific monooxygenase, with EC number 1.14.14.1 Full crystallographic information is available from OCA.
Reference
The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-A resolution., Wester MR, Yano JK, Schoch GA, Yang C, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2004 Aug 20;279(34):35630-7. Epub 2004 Jun 4. PMID:15181000
Page seeded by OCA on Thu Feb 21 14:48:33 2008
Categories: Homo sapiens | Single protein | Unspecific monooxygenase | Griffin, K J. | Johnson, E F. | Schoch, G A. | Stout, C D. | Wester, M R. | Yano, J K. | FLP | GOL | HEM | Drug metabolizing enzyme | Heme | Monooxygenase | Oxidoreductase | P450
