title: Electron transfer activation of chromopyrrolic acid by cytochrome p450 en route to the formation of an antitumor indolocarbazole derivative: theory supports experiment.
abstract: QM/MM calculations support experiment and show that StaP is a P450 that functions like a peroxidase: its active species is the one-electron-reduced Cpd II species with a radical on CPA, by analogy to cytochrome c peroxidase (CcP), and its reaction with the substrate proceeds by overall proton-coupled electron transfer (PCET), in analogy to the corresponding mechanism in horseradish peroxidase (HRP). The electron transfer is enabled by His250, the presence of carboxylate groups in CPA, and by the H-bonding network that tunes the energetic of the process. Theory supports experiment but reveals some novel aspects of this unusual P450.
authors.affiliation: The Institute of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirao
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Onaka
authors.forename: Shingo
authors.initials: S
authors.lastname: Nagano
authors.forename: Sason
authors.initials: S
authors.lastname: Shaik
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism; D002227:Carbazoles / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D004583:Electrons; D006860:Hydrogen Bonding; D007211:Indoles / Q000378:metabolism*; D008958:Models, Molecular; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D007211:Indoles; D011758:Pyrroles; D003577:Cytochrome P-450 Enzyme System