2hi4: Difference between revisions
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[[Image:2hi4.gif|left|200px]] | [[Image:2hi4.gif|left|200px]] | ||
'''Crystal Structure of Human Microsomal P450 1A2 in complex with alpha-naphthoflavone''' | {{Structure | ||
|PDB= 2hi4 |SIZE=350|CAPTION= <scene name='initialview01'>2hi4</scene>, resolution 1.950Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> and <scene name='pdbligand=BHF:2-PHENYL-4H-BENZO[H]CHROMEN-4-ONE'>BHF</scene> | |||
|ACTIVITY= [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] | |||
|GENE= CYP1A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal Structure of Human Microsomal P450 1A2 in complex with alpha-naphthoflavone''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2HI4 is a [ | 2HI4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HI4 OCA]. | ||
==Reference== | ==Reference== | ||
Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2., Sansen S, Yano JK, Reynald RL, Schoch GA, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2007 May 11;282(19):14348-55. Epub 2007 Feb 20. PMID:[http:// | Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2., Sansen S, Yano JK, Reynald RL, Schoch GA, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2007 May 11;282(19):14348-55. Epub 2007 Feb 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17311915 17311915] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: p450 1a2]] | [[Category: p450 1a2]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:17:23 2008'' | ||
Revision as of 18:17, 20 March 2008
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| , resolution 1.950Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | CYP1A2 (Homo sapiens) | ||||||
| Activity: | Unspecific monooxygenase, with EC number 1.14.14.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Human Microsomal P450 1A2 in complex with alpha-naphthoflavone
OverviewOverview
Microsomal cytochrome P450 family 1 enzymes play prominent roles in xenobiotic detoxication and procarcinogen activation. P450 1A2 is the principal cytochrome P450 family 1 enzyme expressed in human liver and participates extensively in drug oxidations. This enzyme is also of great importance in the bioactivation of mutagens, including the N-hydroxylation of arylamines. P450-catalyzed reactions involve a wide range of substrates, and this versatility is reflected in a structural diversity evident in the active sites of available P450 structures. Here, we present the structure of human P450 1A2 in complex with the inhibitor alpha-naphthoflavone, determined to a resolution of 1.95 A. alpha-Naphthoflavone is bound in the active site above the distal surface of the heme prosthetic group. The structure reveals a compact, closed active site cavity that is highly adapted for the positioning and oxidation of relatively large, planar substrates. This unique topology is clearly distinct from known active site architectures of P450 family 2 and 3 enzymes and demonstrates how P450 family 1 enzymes have evolved to catalyze efficiently polycyclic aromatic hydrocarbon oxidation. This report provides the first structure of a microsomal P450 from family 1 and offers a template to study further structure-function relationships of alternative substrates and other cytochrome P450 family 1 members.
About this StructureAbout this Structure
2HI4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2., Sansen S, Yano JK, Reynald RL, Schoch GA, Griffin KJ, Stout CD, Johnson EF, J Biol Chem. 2007 May 11;282(19):14348-55. Epub 2007 Feb 20. PMID:17311915
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