1tqn: Difference between revisions
New page: left|200px<br /> <applet load="1tqn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tqn, resolution 2.05Å" /> '''Crystal Structure o... |
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[[Image:1tqn.gif|left|200px]]<br /> | [[Image:1tqn.gif|left|200px]]<br /><applet load="1tqn" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1tqn, resolution 2.05Å" /> | caption="1tqn, resolution 2.05Å" /> | ||
'''Crystal Structure of Human Microsomal P450 3A4'''<br /> | '''Crystal Structure of Human Microsomal P450 3A4'''<br /> | ||
==Overview== | ==Overview== | ||
The structure of P450 3A4 was determined by x-ray crystallography to | The structure of P450 3A4 was determined by x-ray crystallography to 2.05-A resolution. P450 3A4 catalyzes the metabolic clearance of a large number of clinically used drugs, and a number of adverse drug-drug interactions reflect the inhibition or induction of the enzyme. P450 3A4 exhibits a relatively large substrate-binding cavity that is consistent with its capacity to oxidize bulky substrates such as cyclosporin, statins, taxanes, and macrolide antibiotics. Family 3A P450s also exhibit unusual kinetic characteristics that suggest simultaneous occupancy by smaller substrates. Although the active site volume is similar to that of P450 2C8 (PDB code: 1PQ2), the shape of the active site cavity differs considerably due to differences in the folding and packing of portions of the protein that form the cavity. Compared with P450 2C8, the active site cavity of 3A4 is much larger near the heme iron. The lower constraints on the motions of small substrates near the site of oxygen activation may diminish the efficiency of substrate oxidation, which may, in turn, be improved by space restrictions imposed by the presence of a second substrate molecule. The structure of P450 3A4 should facilitate a better understanding of the substrate selectivity of the enzyme. | ||
==About this Structure== | ==About this Structure== | ||
1TQN 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 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | 1TQN 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> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1TQN 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: HEM]] | [[Category: HEM]] | ||
[[Category: cyp3a4]] | [[Category: cyp3a4]] | ||
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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 15:16:19 2008'' | ||
Revision as of 16:16, 21 February 2008
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Crystal Structure of Human Microsomal P450 3A4
OverviewOverview
The structure of P450 3A4 was determined by x-ray crystallography to 2.05-A resolution. P450 3A4 catalyzes the metabolic clearance of a large number of clinically used drugs, and a number of adverse drug-drug interactions reflect the inhibition or induction of the enzyme. P450 3A4 exhibits a relatively large substrate-binding cavity that is consistent with its capacity to oxidize bulky substrates such as cyclosporin, statins, taxanes, and macrolide antibiotics. Family 3A P450s also exhibit unusual kinetic characteristics that suggest simultaneous occupancy by smaller substrates. Although the active site volume is similar to that of P450 2C8 (PDB code: 1PQ2), the shape of the active site cavity differs considerably due to differences in the folding and packing of portions of the protein that form the cavity. Compared with P450 2C8, the active site cavity of 3A4 is much larger near the heme iron. The lower constraints on the motions of small substrates near the site of oxygen activation may diminish the efficiency of substrate oxidation, which may, in turn, be improved by space restrictions imposed by the presence of a second substrate molecule. The structure of P450 3A4 should facilitate a better understanding of the substrate selectivity of the enzyme.
About this StructureAbout this Structure
1TQN is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Unspecific monooxygenase, with EC number 1.14.14.1 Full crystallographic information is available from OCA.
ReferenceReference
The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution., Yano JK, Wester MR, Schoch GA, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2004 Sep 10;279(37):38091-4. Epub 2004 Jul 16. PMID:15258162
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