Differential Effects of Clotrimazole on X-Ray Crystal Structures of Human Cytochromes P450 3A5 and 3A4

Cytochromes P450 CYP3A5 and CYP3A4 exhibit differential plasticity that underlies differences in drug metabolism and drug-drug interactions. To extend previous studies, CYP3A4 and CYP3A5 were cocrystallized with clotrimazole, a compact ligand that binds to the heme iron in the catalytic center of th...

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Bibliographic Details
Published in:Drug metabolism and disposition 2023-12, Vol.51 (12), p.1642-1650
Main Authors: Hsu, Mei-Hui, Johnson, Eric F
Format: Article
Language:English
Subjects:
Clotrimazole - metabolism
Cytochrome P-450 CYP3A - metabolism
Heme
Humans
Iron
Phenylalanine
X-Rays
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Summary:Cytochromes P450 CYP3A5 and CYP3A4 exhibit differential plasticity that underlies differences in drug metabolism and drug-drug interactions. To extend previous studies, CYP3A4 and CYP3A5 were cocrystallized with clotrimazole, a compact ligand that binds to the heme iron in the catalytic center of the active site. Binding studies indicate that clotrimazole exhibits tight binding to CYP3A5 with a binding affinity (Kd) of
ISSN:0090-9556
1521-009X
1521-009X
DOI:10.1124/dmd.123.001464