Mutations at the distal and proximal sites of cytochrome P-450d changed regio-specificity of acetanilide hydroxylations.
Regio-specificities of acetanilide hydroxylations were studied for 11 distal, 9 proximal and 3 aromatic mutants of cytochrome P-450d. Ratios of turnover numbers among these products were remarkably changed depending on the mutants. For example, the ratio of turnover number, para:ortho:meta = 7:0.1:0.3 for the wild type changed to 11:4:3 for a distal mutant, Thr322Ala, or to 13:13:1 for a proximal mutant, Arg455Gly. It was suggested that regio-specificities of microsomal P-450 enzymes are controlled cooperatively by the whole structure of the protein molecules which influences the tertiary structure of the distal environment.
Furuya
H
H
Chemical Research Institute of Non-Aqueous Solutions, Tohoku University, Sendai, Japan.
Shimizu
T
T
Hatano
M
M
Fujii-Kuriyama
Y
Y
D000083:Acetanilides; D000596:Amino Acids / Q000235:genetics; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006900:Hydroxylation; D051379:Mice; D009154:Mutation; D051381:Rats
D000083:Acetanilides; D000596:Amino Acids; D003577:Cytochrome P-450 Enzyme System