View source for 2p85


==Structure of Human Lung Cytochrome P450 2A13 with indole bound in two alternate conformations==
<StructureSection load='2p85' size='340' side='right'caption='[[2p85]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2p85]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P85 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IND:INDOLE'>IND</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2A13 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Unspecific_monooxygenase Unspecific monooxygenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.14.1 1.14.14.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p85 OCA], [https://pdbe.org/2p85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p85 RCSB], [https://www.ebi.ac.uk/pdbsum/2p85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p85 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/CP2AD_HUMAN CP2AD_HUMAN]] Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.<ref>PMID:18779312</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p8/2p85_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2p85 ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:17428784</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Unspecific monooxygenase]]
[[Category: Scott, E E]]
[[Category: Stout, C D]]
[[Category: Coumarine 7-hydroxylase]]
[[Category: Cyp2a13]]
[[Category: Heme]]
[[Category: Monooxygenase]]
[[Category: Nicotine oxidase]]
[[Category: Nnk oxidase]]
[[Category: Oxidoreductase]]
[[Category: P450]]
[[Category: P450 2a13]]