Characterization of the CYP3A4 Active Site by Homology Modeling
نویسندگان
چکیده
منابع مشابه
Characterization of the CYP3A4 active site by homology modeling.
Human microsomal cytochrome P450s participate in drug metabolism and detoxification. Among them, CYP3A4 is the most important isoform for drug-drug interactions. To gain a better understanding of the active site, a homology model of CYP3A4 was constructed based on the crystallographic coordinates of mammalian CYP2C5. The putative active site is much larger than that of CYP2C5 and is divided int...
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The leucine 211 --> phenylalanine (L211F) and leucine 211 --> tyrosine (L211Y) mutant forms of cytochrome P450 3A4 have been generated by site-directed mutagenesis and expressed functionally in Escherichia coli. Substrate binding affinities (S50 values) for testosterone and 7-benzyloxy-4-trifluoromethylcoumarin (BFC) were similar for the mutants and wild-type CYP3A4 (49 and 21 microM for L211F,...
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A reliable model of tobacco acetohydroxy acid synthase (AHAS) was obtained by homology modeling based on a yeast AHAS X-ray structure using the Swiss-Model server. Conserved residues at the dimer interface were identified, of which the functional roles of four residues, namely H142, E143, M489, and M542, were determined by site-directed mutagenesis. Eight mutants were successfully generated and...
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Phenyldiazene reacted with lymphoblast-expressed CYP3A4 to give a stable phenyl-iron complex that could be induced to rearrange in situ producing approximately equal amounts of four N-phenyl-protoporphyrin IX isomers (N(B):N(A):N(C):N(D), 01:01:02:02). In the presence of 10 mM MgCl(2), the formation profile of the protoporphyrin isomers was markedly altered compared with control, favoring the N...
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Phenyldiazene reacted with lymphoblast-expressed CYP3A4 to give a stable phenyl-iron complex that could be induced to rearrange in situ producing approximately equal amounts of four Nphenyl-protoporphyrin IX isomers (NB:NA:NC:ND, 01:01:02:02). In the presence of 10 mM MgCl2, the formation profile of the protoporphyrin isomers was markedly altered compared with control, favoring the NA isomer (N...
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ژورنال
عنوان ژورنال: CHEMICAL & PHARMACEUTICAL BULLETIN
سال: 2004
ISSN: 0009-2363,1347-5223
DOI: 10.1248/cpb.52.830