Cytochrome P450. The Dioxygen-Activating Heme Thiolate.

Abstract

Cytochromes P450 (CYPs) are heme b-binding enzymes and belong to Nature's most versatile catalysts. They participate in countless essential life processes, and exist in all domains of life, Bacteria, Archaea, and Eukarya, and in viruses. CYPs attract the interest of researchers active in fields as diverse as biochemistry, chemistry, biophysics, molecular biology, pharmacology, and toxicology. CYPs fight chemicals such as drugs, poisonous compounds in plants, carcinogens formed during cooking, and environmental pollutants. They represent the first line of defense to detoxify and solubilize poisonous substances by modifying them with dioxygen. The heme iron is proximally coordinated by a thiolate residue, and this ligation state represents the active form of the enzyme. The Fe(III) center displays characteristic UV/Vis and EPR spectra (Soret maximum at 418 nm; g-values at 2.41, 2.26, 1.91). The Fe(II) state binds the inhibitor carbon monoxide (CO) to produce a Fe(II)-CO complex, with the major absorption maximum at 450 nm, hence, its name P450. CYPs are flexible proteins in order to allow a vast range of substrates to enter and products to leave. Two extreme forms exist: substrate-bound (closed) and substrate-free (open). CYPs share a sophisticated catalytic cycle that involves a series of consecutive transformations of the heme thiolate active site, with the strong oxidants compound I and II as key intermediates. Each of these high-valent Fe(IV) species has its characteristic features and chemical properties, crucial for the activation of dioxygen and cleavage of strong C-H bonds.