2pg7
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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 with as ligand. Active as Unspecific monooxygenase, with EC number 1.14.14.1 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 May 11;. PMID:17540336
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