2pg5

From Proteopedia

(Difference between revisions)

Revision as of 01:11, 10 September 2015

Crystal Structure of Human Microsomal P450 2A6 N297Q

Structural highlights

2pg5 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1z10, 1z11, 2fdu, 2fdv, 2fdw, 2fdy, 2pg6, 2pg7
Gene:	CYP2A6 (HUMAN)
Activity:	Unspecific monooxygenase, with EC number 1.14.14.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Maurice M, Emiliani S, Dalet-Beluche I, Derancourt J, Lange R. Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. Eur J Biochem. 1991 Sep 1;200(2):511-7. PMID:1889415
↑ Yun CH, Shimada T, Guengerich FP. Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol. 1991 Nov;40(5):679-85. PMID:1944238
↑ Miyazawa M, Shindo M, Shimada T. Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica. 2001 Oct;31(10):713-23. PMID:11695850 doi:10.1080/00498250110065595
↑ Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol. 2005 Sep;12(9):822-3. Epub 2005 Aug 7. PMID:16086027 doi:http://dx.doi.org/10.1038/nsmb971
↑ Yano JK, Denton TT, Cerny MA, Zhang X, Johnson EF, Cashman JR. Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization. J Med Chem. 2006 Nov 30;49(24):6987-7001. PMID:17125252 doi:http://dx.doi.org/10.1021/jm060519r
↑ DeVore NM, Smith BD, Urban MJ, Scott EE. Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes. Drug Metab Dispos. 2008 Dec;36(12):2582-90. Epub 2008 Sep 8. PMID:18779312 doi:10.1124/dmd.108.023770
↑ Sansen S, Hsu MH, Stout CD, Johnson EF. Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants. Arch Biochem Biophys. 2007 Aug 15;464(2):197-206. Epub 2007 May 11. PMID:17540336 doi:10.1016/j.abb.2007.04.028

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pg5"

@@ Line 2: / Line 2: @@
 <StructureSection load='2pg5' size='340' side='right' caption='[[2pg5]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2pg5]] is a 4 chain structure with 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PG5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2pg5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PG5 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1z10|1z10]], [[1z11|1z11]], [[2fdu|2fdu]], [[2fdv|2fdv]], [[2fdw|2fdw]], [[2fdy|2fdy]], [[2pg6|2pg6]], [[2pg7|2pg7]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2A6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP2A6 ([http://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'>[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] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pg5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pg5 RCSB], [http://www.ebi.ac.uk/pdbsum/2pg5 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pg5 OCA], [http://pdbe.org/2pg5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pg5 RCSB], [http://www.ebi.ac.uk/pdbsum/2pg5 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 29: / Line 29: @@
 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>
 ==See Also==
@@ Line 36: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Unspecific monooxygenase]]
 [[Category: Hsu, M H]]

2pg5

From Proteopedia

Revision as of 01:11, 10 September 2015

Crystal Structure of Human Microsomal P450 2A6 N297Q

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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