2pg5: Difference between revisions

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{{Seed}}
[[Image:2pg5.png|left|200px]]


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==Crystal Structure of Human Microsomal P450 2A6 N297Q==
The line below this paragraph, containing "STRUCTURE_2pg5", creates the "Structure Box" on the page.
<StructureSection load='2pg5' size='340' side='right'caption='[[2pg5]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2pg5]] 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=2PG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PG5 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
{{STRUCTURE_2pg5|  PDB=2pg5  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pg5 OCA], [https://pdbe.org/2pg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pg5 RCSB], [https://www.ebi.ac.uk/pdbsum/2pg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pg5 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/pg/2pg5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2pg5 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human P450 2A6 displays a small active site that is well adapted for the oxidation of small planar substrates. Mutagenesis of CYP2A6 resulted in an increased catalytic efficiency for indole biotransformation to pigments and conferred a capacity to oxidize substituted indoles (Wu, Z.-L., Podust, L.M., Guengerich, F.P. J. Biol. Chem. 49 (2005) 41090-41100.). Here, we describe the structural basis that underlies the altered metabolic profile of three mutant enzymes, P450 2A6 N297Q, L240C/N297Q and N297Q/I300V. The Asn297 substitution abolishes a potential hydrogen bonding interaction with substrates in the active site, and replaces a structural water molecule between the helix B'-C region and helix I while maintaining structural hydrogen bonding interactions. The structures of the P450 2A6 N297Q/L240C and N297Q/I300V mutants provide clues as to how the protein can adapt to fit the larger substituted indoles in the active site, and enable a comparison with other P450 family 2 enzymes for which the residue at the equivalent position was seen to function in isozyme specificity, structural integrity and protein flexibility.


===Crystal Structure of Human Microsomal P450 2A6 N297Q===
Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants.,Sansen S, Hsu MH, Stout CD, Johnson EF Arch Biochem Biophys. 2007 Aug 15;464(2):197-206. Epub 2007 May 11. PMID:17540336<ref>PMID:17540336</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2pg5" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_17540336}}, adds the Publication Abstract to the page
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 17540336 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_17540336}}
__TOC__
 
</StructureSection>
==About this Structure==
2PG5 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=2PG5 OCA].
 
==Reference==
Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants., Sansen S, Hsu MH, Stout CD, Johnson EF, Arch Biochem Biophys. 2007 Aug 15;464(2):197-206. Epub 2007 May 11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17540336 17540336]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Unspecific monooxygenase]]
[[Category: Hsu MH]]
[[Category: Hsu, M H.]]
[[Category: Johnson EF]]
[[Category: Johnson, E F.]]
[[Category: Sansen S]]
[[Category: Sansen, S.]]
[[Category: Stout CD]]
[[Category: Stout, C D.]]
[[Category: Cyp2a6]]
[[Category: Drug metabolizing enzyme]]
[[Category: Heme]]
[[Category: Indole]]
[[Category: Monooxygenase]]
[[Category: Mutant]]
[[Category: P450]]
[[Category: P450 2a6]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:02:50 2008''

Latest revision as of 08:28, 13 August 2026

Crystal Structure of Human Microsomal P450 2A6 N297Q

2pg5, resolution 1.95Å

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