2pg7: Difference between revisions

Revision as of 13:03, 4 May 2008

Crystal Structure of Human Microsomal P450 2A6 N297Q/I300V

OverviewOverview

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 StructureAbout this Structure

2PG7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 13:03:02 2008

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OCA

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 [[Image:2pg7.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2pg7", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <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>
+or leave the SCENE parameter empty for the default display.
-|GENE= CYP2A6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2pg7|  PDB=2pg7  |  SCENE=  }}
-|RELATEDENTRY=[[1z10|1Z10]], [[1z11|1Z11]], [[2fdu|2FDU]], [[2fdv|2FDV]], [[2fdw|2FDW]], [[2fdy|2FDY]], [[2pg5|2PG5]], [[2pg6|2PG6]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pg7 OCA], [http://www.ebi.ac.uk/pdbsum/2pg7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2pg7 RCSB]</span>
-}}
 '''Crystal Structure of Human Microsomal P450 2A6 N297Q/I300V'''
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 [[Category: Sansen, S.]]
 [[Category: Stout, C D.]]
-[[Category: cyp2a6]]
+[[Category: Cyp2a6]]
-[[Category: drug metabolizing enzyme]]
+[[Category: Drug metabolizing enzyme]]
-[[Category: heme]]
+[[Category: Heme]]
-[[Category: indole]]
+[[Category: Indole]]
-[[Category: monooxygenase]]
+[[Category: Monooxygenase]]
-[[Category: mutant]]
+[[Category: Mutant]]
-[[Category: p450]]
+[[Category: P450]]
-[[Category: p450 2a6]]
+[[Category: P450 2a6]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 13:03:02 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:35:29 2008''