Defining the Structural Consequences of Mechanism-Based Inactivation of Mammalian Cytochrome P450 2B4 Using Resonance Raman Spectroscopy

摘要

Membrane-bound human cytochromes P450, which are responsible for catalyzing the metabolism of Pharmaceuticals or other xenobiotics, proceed through a complex cycle involving the sequential delivery of two electrons to a heme-bound dioxygen complex, effecting the splitting of the O-O bond to generate a potent oxygenating intermediate capable of inserting a single oxygen atom into the bound substrates, the nature of the putative intermediate generally being formulated as a ferryl heme π-cation similar to the Compound I species in the enzymatic cycles of the heme peroxidases.