title: The elusive oxidant species of cytochrome P450 enzymes: characterization by combined quantum mechanical/molecular mechanical (QM/MM) calculations.
abstract: The primary oxidant of cytochrome P450 enzymes, Compound I, is hard to detect experimentally; in the case of cytochrome P450(cam), this intermediate does not accumulate in solution during the catalytic cycle even at temperatures as low as 200 K (ref 4). Theory can play an important role in characterizing such elusive species. We present here combined quantum mechanical/molecular mechanical (QM/MM) calculations of Compound I of cytochrome P450(cam) in the full enzyme environment as well as density functional studies of the isolated QM region. The calculations assign the ground state of the species, quantify the effect of polarization and hydrogen bonding on its properties, and show that the protein environment and its specific hydrogen bonding to the cysteinate ligand are crucial for sustaining the Fe-S bond and for preventing the full oxidation of the sulfur.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Schöneboom
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Reuter
authors.forename: Walter
authors.initials: W
authors.lastname: Thiel
authors.forename: Shimrit
authors.initials: S
authors.lastname: Cohen
authors.forename: François
authors.initials: F
authors.lastname: Ogliaro
authors.forename: Sason
authors.initials: S
authors.lastname: Shaik
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D016877:Oxidants / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D016877:Oxidants; D003577:Cytochrome P-450 Enzyme System