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PDBsum entry 2pg7
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Oxidoreductase
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PDB id
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2pg7
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References listed in PDB file
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Key reference
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Title
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Structural insight into the altered substrate specificity of human cytochrome p450 2a6 mutants.
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Authors
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S.Sansen,
M.H.Hsu,
C.D.Stout,
E.F.Johnson.
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Ref.
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Arch Biochem Biophys, 2007,
464,
197-206.
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PubMed id
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Abstract
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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.
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