1z11: Difference between revisions

No edit summary
No edit summary
 
(11 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1z11.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_1z11", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1z11|  PDB=1z11  |  SCENE=  }}
'''Crystal Structure of Human Microsomal P450 2A6 with Methoxsalen Bound'''


==Crystal Structure of Human Microsomal P450 2A6 with Methoxsalen Bound==
<StructureSection load='1z11' size='340' side='right'caption='[[1z11]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1z11]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z11 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8MO:METHOXSALEN'>8MO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></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=1z11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z11 OCA], [https://pdbe.org/1z11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z11 RCSB], [https://www.ebi.ac.uk/pdbsum/1z11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z11 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CP2A6_HUMAN CP2A6_HUMAN] Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.<ref>PMID:1889415</ref> <ref>PMID:1944238</ref> <ref>PMID:11695850</ref> <ref>PMID:16086027</ref> <ref>PMID:17125252</ref> <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/z1/1z11_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=1z11 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human microsomal cytochrome P450 2A6 (CYP2A6) contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. The CYP2A6 structure shows a compact, hydrophobic active site with one hydrogen bond donor, Asn297, that orients coumarin for regioselective oxidation. The inhibitor methoxsalen effectively fills the active site cavity without substantially perturbing the structure. The structure should aid the design of inhibitors to reduce smoking and tobacco-related cancers.


==Overview==
Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen.,Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF Nat Struct Mol Biol. 2005 Sep;12(9):822-3. Epub 2005 Aug 7. PMID:16086027<ref>PMID:16086027</ref>
Human microsomal cytochrome P450 2A6 (CYP2A6) contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. The CYP2A6 structure shows a compact, hydrophobic active site with one hydrogen bond donor, Asn297, that orients coumarin for regioselective oxidation. The inhibitor methoxsalen effectively fills the active site cavity without substantially perturbing the structure. The structure should aid the design of inhibitors to reduce smoking and tobacco-related cancers.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1Z11 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=1Z11 OCA].
</div>
<div class="pdbe-citations 1z11" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen., Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF, Nat Struct Mol Biol. 2005 Sep;12(9):822-3. Epub 2005 Aug 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16086027 16086027]
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Unspecific monooxygenase]]
[[Category: Griffin KJ]]
[[Category: Griffin, K J.]]
[[Category: Hsu MH]]
[[Category: Hsu, M H.]]
[[Category: Johnson EF]]
[[Category: Johnson, E F.]]
[[Category: Stout CD]]
[[Category: Stout, C D.]]
[[Category: Yano JK]]
[[Category: Yano, J K.]]
[[Category: Coumarin 7-hydroxylase]]
[[Category: Cyp2a6]]
[[Category: Drug metabolizing enzyme]]
[[Category: Heme]]
[[Category: Methoxsalen]]
[[Category: Monooxygenase]]
[[Category: Nicotine oxidase]]
[[Category: Oxidoreductase]]
[[Category: P450]]
[[Category: P450 2a6]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 17:03:21 2008''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA