Significant Increase in Phenacetin Oxidation on L382V Substitution in Human Cytochrome P450 1A2

Significant increase in phenacetin oxidation on L382V substitution in human cytochrome P450 1A2.

Human CYP1A2 is an important drug-metabolizing enzyme, similar in sequence to CYP1A1 but with distinct substrate specificity. We have previously shown that residue 382 affected CYP1A1 and CYP1A2 specificities with alkoxyresorufins. To determine whether this residue is also important for the metabolism of other substrates, we have investigated phenacetin oxidation by single (T124S, T223N, V227G,...

Significant Increase in Phenacetin Oxidation upon Leu - 382 → Val Substitution in Human Cytochrome P 450 1 A 2

Co-expression of active human cytochrome P450 1A2 and cytochrome P450 reductase on the cell surface of Escherichia coli

BACKGROUND Human cytochrome P450 (CYP) enzymes mediate the first step in the breakdown of most drugs and are strongly involved in drug-drug interactions, drug clearance and activation of prodrugs. Their biocatalytic behavior is a key parameter during drug development which requires preparative synthesis of CYP related drug metabolites. However, recombinant expression of CYP enzymes is a challen...

Cytochrome P450 1A2 detoxicates aristolochic acid in the mouse.

Aristolochic acids (AAs) are plant-derived nephrotoxins and carcinogens responsible for chronic renal failure and associated urothelial cell cancers in several clinical syndromes known collectively as aristolochic acid nephropathy (AAN). Mice provide a useful model for study of AAN because the renal histopathology of AA-treated mice is strikingly similar to that of humans. AA is also a potent c...

Cross-Linking study of cytochrome P450 1A2 in proteoliposomes.

Proteoliposomes, containing cytochrome P450 1A2, were obtained by the cholate-dialysis technique. The effect of bifunctional cross-linking reagents on the purified hexameric cytochrome P450 1A2 in an aqueous medium and on the proteoliposomal P450 1A2 have been compared. Electrophoretic analysis of the modified proteins demonstrated the same oligomeric (hexameric) organization of the hemoprotein...