2PG7
Crystal Structure of Human Microsomal P450 2A6 N297Q/I300V
Summary for 2PG7
Entry DOI | 10.2210/pdb2pg7/pdb |
Related | 1Z10 1Z11 2FDU 2FDV 2FDW 2FDY 2PG5 2PG6 |
Descriptor | Cytochrome P450 2A6, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total) |
Functional Keywords | cyp2a6, p450 2a6, p450, monooxygenases, drug metabolizing enzyme, heme, indole, mutant, oxidoreductase |
Biological source | Homo sapiens (human) |
Cellular location | Endoplasmic reticulum membrane; Peripheral membrane protein: P11509 |
Total number of polymer chains | 4 |
Total formula weight | 221152.50 |
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 citation | Sansen, 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: 17540336DOI: 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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