2p85
From Proteopedia
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| - | [[Image:2p85.gif|left|200px]] | + | [[Image:2p85.gif|left|200px]] |
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| - | '''Structure of Human Lung Cytochrome P450 2A13 with indole bound in two alternate conformations''' | + | {{Structure |
| + | |PDB= 2p85 |SIZE=350|CAPTION= <scene name='initialview01'>2p85</scene>, resolution 2.35Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene> and <scene name='pdbligand=IND:INDOLE'>IND</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= CYP2A13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structure of Human Lung Cytochrome P450 2A13 with indole bound in two alternate conformations''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2P85 is a [ | + | 2P85 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=2P85 OCA]. |
==Reference== | ==Reference== | ||
| - | Structure of the human lung cytochrome P450 2A13., Smith BD, Sanders JL, Porubsky PR, Lushington GH, Stout CD, Scott EE, J Biol Chem. 2007 Jun 8;282(23):17306-13. Epub 2007 Apr 11. PMID:[http:// | + | Structure of the human lung cytochrome P450 2A13., Smith BD, Sanders JL, Porubsky PR, Lushington GH, Stout CD, Scott EE, J Biol Chem. 2007 Jun 8;282(23):17306-13. Epub 2007 Apr 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17428784 17428784] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: p450 2a13]] | [[Category: p450 2a13]] | ||
| - | ''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 18:09:55 2008'' |
Revision as of 16:09, 20 March 2008
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| , resolution 2.35Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | CYP2A13 (Homo sapiens) | ||||||
| Activity: | Unspecific monooxygenase, with EC number 1.14.14.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of Human Lung Cytochrome P450 2A13 with indole bound in two alternate conformations
Overview
The human lung cytochrome P450 2A13 (CYP2A13) activates the nicotine-derived procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) into DNA-altering compounds that cause lung cancer. Another cytochrome P450, CYP2A6, is also present in human lung, but at much lower levels. Although these two enzymes are 93.5% identical, CYP2A13 metabolizes NNK with much lower K(m) values than does CYP2A6. To investigate the structural differences between these two enzymes the structure of CYP2A13 was determined to 2.35A by x-ray crystallography and compared with structures of CYP2A6. As expected, the overall CYP2A13 and CYP2A6 structures are very similar with an average root mean square deviation of 0.5A for the Calpha atoms. Like CYP2A6, the CYP2A13 active site cavity is small and highly hydrophobic with a cluster of Phe residues composing the active site roof. Active site residue Asn(297) is positioned to hydrogen bond with an adventitious ligand, identified as indole. Amino acid differences between CYP2A6 and CYP2A13 at positions 117, 300, 301, and 208 relate to different orientations of the ligand plane in the two protein structures and may underlie the significant variations observed in binding and catalysis of many CYP2A ligands. In addition, docking studies suggest that residues 365 and 366 may also contribute to differences in NNK metabolism.
About this Structure
2P85 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the human lung cytochrome P450 2A13., Smith BD, Sanders JL, Porubsky PR, Lushington GH, Stout CD, Scott EE, J Biol Chem. 2007 Jun 8;282(23):17306-13. Epub 2007 Apr 11. PMID:17428784
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