Cytochromes P450 are a superfamily of cysteine thiolate-ligated heme-containing monooxygenase enzymes that catalyze the transfer of an oxygen atom from molecular oxygen into a wide variety of biological substrates, with the second oxygen atom being reduced by two electrons to a water molecule (Equation (1)).1–10 Cytochrome P450 enzymes have been isolated from mammalian tissues, birds, fish, plants, insects, yeasts, bacteria, and other biological species, and the monooxygenases are known to participate in drug metabolism, biotransformation of naturally occurring molecules, and oxidative metabolism of xenobiotics.8–10 The most often-encountered oxidation reactions by cytochromes P450 are hydroxylation, epoxidation, heteroatom oxidation, and heteroatom dealkylation: (Formula Presented) The first three-dimensional structure of cytochrome P450 was reported by Poulos in 1985, the soluble bacterial cytochrome P450cam isolated from the bacterium Pseudomonas putida.11 The enzyme, which catalyzes the stereospecific hydroxylation of camphor to 5-exo-hydroxycamphor (Equation (2)), consists of a single polypeptide chain containing a heme b group (iron protoporphyrin IX) with a cysteine, Cys357, as an axial ligand (Figure 1). The heme b group bound to the protein by an iron-cysteinate bond is deeply embedded in the hydrophobic interior (Formula Presented) Fe to accommodate hydrophobic substrates. The name cytochrome P450 is derived from the fact that a red-shifted strong Soret band (high-energy π–π* transition of the porphyrin ring) appears at 450 nm when CO binds to ferrous heme (FeII-CO). This spectral feature is caused by the strong electron-donating character of the cysteinate proximal ligand.12,13 Other heme-containing proteins bearing a histidine proximal ligand exhibit a....
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