Interaction between cytochrome P450 2B1 and cytochrome bs: inhibition by synthetic peptides indicates a role for P450 residues Lys-122 and Arg-125.
Binding of cytochrome b5 to rat cytochrome P450 2B1 was inhibited (by 75%) by a synthetic peptide corresponding to P450 residues 116-134. The role of Lys-122 and Arg-125 were evaluated using peptides in which one or both of these basic residues were replaced with Glu. The Lys-122 substitution nearly abolished while the Arg-125 replacement decreased (by 20%) the inhibitory potential of the peptide. Substitution of both residues resulted in a peptide with no inhibitory activity. These results thus indicate a role for a specific P450 region as well as two basic residues within this region in the cytochrome P450-cytochrome b5 interaction.
Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Y
Y
Omata
H
H
Sakamoto
R C
RC
Robinson
M R
MR
Pincus
F K
FK
Friedman
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000737:chemistry / Q000378:metabolism*
D010455:Peptides; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase; D008239:Lysine