Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2.
作者： Stefaan Sansen , Jason K. Yano , Rosamund L. Reynald , Guillaume A. Schoch , Keith J. Griffin
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摘要: Microsomal cytochrome P450 family 1 enzymes play prominent roles in xenobiotic detoxication and procarcinogen activation. 1A2 is the principal enzyme expressed human liver participates extensively drug oxidations. This also of great importance bioactivation mutagens, including N-hydroxylation arylamines. P450-catalyzed reactions involve a wide range substrates, this versatility reflected structural diversity evident active sites available structures. Here, we present structure complex with inhibitor alpha-naphthoflavone, determined to resolution 1.95 A. alpha-Naphthoflavone bound site above distal surface heme prosthetic group. The reveals compact, closed cavity that highly adapted for positioning oxidation relatively large, planar substrates. unique topology clearly distinct from known architectures 2 3 demonstrates how have evolved catalyze efficiently polycyclic aromatic hydrocarbon oxidation. report provides first microsomal offers template study further structure-function relationships alternative substrates other members.
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