Formation of a Novel Reversible Cytochrome P450 Spectral Intermediate:

The cytochrome P450 enzymes belong to a superfamily of heme-containing mono-oxygenases that are involved in the metabolism of numerous endogenous and exogenous substrates. The ethanol-inducible cytochrome P450 2E1 catalyzes the oxidation of a large number of drugs and hepatotoxic xenobiotics, including halogenated alkanes, acetaminophen, nitrosamines, benzene, and styrene. Evidence from homology models of P450 2E1 and studies in which a conserved threonine residue in the I helix of several different P450s was mutated to an alanine points to a role for this residue in the orientation of substrate in the P450 active site and as a possible proton donor in acid-base reactions. Site-specific mutation of this threonine residue (T303A) in P450 2E1 has allowed for comparisons between wild-type P450 2E1 and the mutant enzyme.

For full article Click Here