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2PG7

Crystal Structure of Human Microsomal P450 2A6 N297Q/I300V

Summary for 2PG7
Entry DOI10.2210/pdb2pg7/pdb
Related1Z10 1Z11 2FDU 2FDV 2FDW 2FDY 2PG5 2PG6
DescriptorCytochrome P450 2A6, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
Functional Keywordscyp2a6, p450 2a6, p450, monooxygenases, drug metabolizing enzyme, heme, indole, mutant, oxidoreductase
Biological sourceHomo sapiens (human)
Cellular locationEndoplasmic reticulum membrane; Peripheral membrane protein: P11509
Total number of polymer chains4
Total formula weight221152.50
Authors
Sansen, S.,Hsu, M.H.,Stout, C.D.,Johnson, E.F. (deposition date: 2007-04-06, release date: 2007-07-24, Last modification date: 2023-08-30)
Primary citationSansen, S.,Hsu, M.H.,Stout, C.D.,Johnson, E.F.
Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants.
Arch.Biochem.Biophys., 464:197-206, 2007
Cited by
PubMed Abstract: 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.
PubMed: 17540336
DOI: 10.1016/j.abb.2007.04.028
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.8 Å)
Structure validation

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