2pg7: Difference between revisions

From Proteopedia
Jump to navigationJump to search
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
New page: left|200px<br /> <applet load="2pg7" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pg7, resolution 2.800Å" /> '''Crystal Structure ...
 
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
(17 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2pg7.gif|left|200px]]<br />
<applet load="2pg7" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2pg7, resolution 2.800&Aring;" />
'''Crystal Structure of Human Microsomal P450 2A6 N297Q/I300V'''<br />


==Overview==
==Crystal Structure of Human Microsomal P450 2A6 N297Q/I300V==
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.
<StructureSection load='2pg7' size='340' side='right'caption='[[2pg7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2pg7]] 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=2PG7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PG7 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]] 2.8&#8491;</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></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=2pg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pg7 OCA], [https://pdbe.org/2pg7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pg7 RCSB], [https://www.ebi.ac.uk/pdbsum/2pg7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pg7 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/2pg7_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=2pg7 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.


==About this Structure==
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>
2PG7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEM as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2PG7 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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 May 11;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17540336 17540336]
</div>
<div class="pdbe-citations 2pg7" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[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: 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: HEM]]
[[Category: cyp2a6]]
[[Category: drug metabolizing enzyme]]
[[Category: heme]]
[[Category: indole]]
[[Category: monooxygenases]]
[[Category: mutant]]
[[Category: p450]]
[[Category: p450 2a6]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:23:28 2007''
Retrieved from "https://proteopedia.org/2pg7"