TY - JOUR
T1 - Active-site topologies of human CYP2D6 and its aspartate-301 → glutamate, asparagine, and glycine mutants
AU - Mackman, Richard
AU - Tschirret-Guth, Richard A.
AU - Smith, Gillian
AU - Hayhurst, Graham P.
AU - Ellis, S. Wynne
AU - Lennard, Martin S.
AU - Tucker, Geoffrey T.
AU - Wolf, C. Roland
AU - Ortiz de Montellano, Paul R.
N1 - This work was supported by National Institutes of Health Grant GM25515 (P.R.O.M.) and the Wellcome Trust Grant 038735 (M.S.L., G.T.T., C.R.W.). Support for the Liver Center core facilities at the University of California, San Francisco, was provided by Grant 5 P30 DK26743
PY - 1996
Y1 - 1996
N2 - Cytochrome P450 2D6 (CYP2D6) catalyzes the oxidation of substrates with a positively charged nitrogen atom 5-7 angstroms from the site of the oxidation. The active-site topology of CYP2D6 is examined here with phenyl-, 2-naphthyl-, and p-biphenyldiazene, which react with P450 enzymes to form sigma-bonded aryl-iron (Fe-Ar) complexes. Ferricyanide-mediated migration of the aryl group from the iron to the porphyrin nitrogens produces the N-arylprotoporphyrin IX regioisomers (NB:NA:NC:ND, in which the aryl group is bound to the nitrogen of pyrrole rings B, A, C, and D, respectively) in the following ratios (zero means
AB - Cytochrome P450 2D6 (CYP2D6) catalyzes the oxidation of substrates with a positively charged nitrogen atom 5-7 angstroms from the site of the oxidation. The active-site topology of CYP2D6 is examined here with phenyl-, 2-naphthyl-, and p-biphenyldiazene, which react with P450 enzymes to form sigma-bonded aryl-iron (Fe-Ar) complexes. Ferricyanide-mediated migration of the aryl group from the iron to the porphyrin nitrogens produces the N-arylprotoporphyrin IX regioisomers (NB:NA:NC:ND, in which the aryl group is bound to the nitrogen of pyrrole rings B, A, C, and D, respectively) in the following ratios (zero means
U2 - 10.1006/abbi.1996.0291
DO - 10.1006/abbi.1996.0291
M3 - Article
C2 - 8660692
VL - 331
SP - 134
EP - 140
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 1
ER -