title: Fatty acid metabolism, conformational change, and electron transfer in cytochrome P-450(BM-3).
abstract: Crystal structure-based mutagenesis studies on cytochrome P-450(BM-3) have confirmed the importance of R47, Y51, and F87 in substrate binding. Replacing F87 has profound effects on regioselectivity. In contrast, changing either R47 or Y51 alone to other residues results in limited impact on substrate binding affinity. Mutating both, however, leads to large changes. Substrate-induced protein conformational changes not only lead to specific substrate binding in the heme domain, but also affect interactions with the FMN domain. Unlike the microsomal P-450 reductase, the FMN semiquinone is the active electron donor to the heme iron in P-450(BM-3). The crystal structure of P-450(BM-3) heme/FMN bidomain provides important insights into why the FMN semiquinone is the preferred electron donor to the heme as well as how substrate-induced structural changes possibly affect the FMN and heme domain-domain interaction.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697-3900, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: T L
authors.initials: TL
authors.lastname: Poulos
mesh_terms: D001410:Bacillus megaterium / Q000201:enzymology; D001426:Bacterial Proteins; D003460:Crystallization; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D004579:Electron Transport; D005227:Fatty Acids / Q000378:metabolism*; D005486:Flavin Mononucleotide / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D016296:Mutagenesis; D009251:NADPH-Ferrihemoprotein Reductase; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D005227:Fatty Acids; D006418:Heme; D005486:Flavin Mononucleotide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases