2f9q
From Proteopedia
(New page: 200px<br /> <applet load="2f9q" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f9q, resolution 3.002Å" /> '''Crystal Structure ...) |
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| - | [[Image:2f9q.gif|left|200px]]<br /> | + | [[Image:2f9q.gif|left|200px]]<br /><applet load="2f9q" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2f9q, resolution 3.002Å" /> | caption="2f9q, resolution 3.002Å" /> | ||
'''Crystal Structure of Human Cytochrome P450 2D6'''<br /> | '''Crystal Structure of Human Cytochrome P450 2D6'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cytochrome P450 2D6 is a heme-containing enzyme that is responsible for | + | Cytochrome P450 2D6 is a heme-containing enzyme that is responsible for the metabolism of at least 20% of known drugs. Substrates of 2D6 typically contain a basic nitrogen and a planar aromatic ring. The crystal structure of human 2D6 has been solved and refined to 3.0A resolution. The structure shows the characteristic P450 fold as seen in other members of the family, with the lengths and orientations of the individual secondary structural elements being very similar to those seen in 2C9. There are, however, several important differences, the most notable involving the F helix, the F-G loop, the B'helix, beta sheet 4, and part of beta sheet 1, all of which are situated on the distal face of the protein. The 2D6 structure has a well defined active site cavity above the heme group, containing many important residues that have been implicated in substrate recognition and binding, including Asp-301, Glu-216, Phe-483, and Phe-120. The crystal structure helps to explain how Asp-301, Glu-216, and Phe-483 can act as substrate binding residues and suggests that the role of Phe-120 is to control the orientation of the aromatic ring found in most substrates with respect to the heme. The structure has been compared with published homology models and has been used to explain much of the reported site-directed mutagenesis data and help understand the metabolism of several compounds. |
==About this Structure== | ==About this Structure== | ||
| - | 2F9Q 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 SO4 and HEM 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:// | + | 2F9Q 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=SO4:'>SO4</scene> and <scene name='pdbligand=HEM:'>HEM</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=2F9Q OCA]. |
==Reference== | ==Reference== | ||
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[[Category: cytochrome p450 2d6; haem]] | [[Category: cytochrome p450 2d6; haem]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:19:10 2008'' |
Revision as of 15:19, 21 February 2008
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Crystal Structure of Human Cytochrome P450 2D6
Overview
Cytochrome P450 2D6 is a heme-containing enzyme that is responsible for the metabolism of at least 20% of known drugs. Substrates of 2D6 typically contain a basic nitrogen and a planar aromatic ring. The crystal structure of human 2D6 has been solved and refined to 3.0A resolution. The structure shows the characteristic P450 fold as seen in other members of the family, with the lengths and orientations of the individual secondary structural elements being very similar to those seen in 2C9. There are, however, several important differences, the most notable involving the F helix, the F-G loop, the B'helix, beta sheet 4, and part of beta sheet 1, all of which are situated on the distal face of the protein. The 2D6 structure has a well defined active site cavity above the heme group, containing many important residues that have been implicated in substrate recognition and binding, including Asp-301, Glu-216, Phe-483, and Phe-120. The crystal structure helps to explain how Asp-301, Glu-216, and Phe-483 can act as substrate binding residues and suggests that the role of Phe-120 is to control the orientation of the aromatic ring found in most substrates with respect to the heme. The structure has been compared with published homology models and has been used to explain much of the reported site-directed mutagenesis data and help understand the metabolism of several compounds.
About this Structure
2F9Q 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
Crystal structure of human cytochrome P450 2D6., Rowland P, Blaney FE, Smyth MG, Jones JJ, Leydon VR, Oxbrow AK, Lewis CJ, Tennant MG, Modi S, Eggleston DS, Chenery RJ, Bridges AM, J Biol Chem. 2006 Mar 17;281(11):7614-22. Epub 2005 Dec 13. PMID:16352597
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