A heme-thiolate enzyme is an enzyme whose heme iron has an axial sulfur ligand supplied by a cysteine thiolate in the protein. This coordination arrangement contributes to the oxygen-activation chemistry of cytochrome P450 enzymes [1]. A high-valent iron–oxo species, compound I, can cleave substrate carbon–hydrogen bonds during the catalytic cycle [2]. Thiolate donation alters the electronic properties of iron-bound oxygen intermediates and helps support the highly reactive species used in substrate oxidation [3]. In many members, successive reduction and protonation steps lead to oxygen–oxygen bond cleavage and formation of a high-valent iron–oxo intermediate. Reaction with the bound substrate then transfers oxygen or removes hydrogen equivalents, with the surrounding protein controlling substrate orientation and access [4].
- cysteine ligation
- heme iron
- peroxygenases
- iron–oxo intermediates
References
- Ilia G. Denisov; Thomas M. Makris; Stephen G. Sligar; Ilme Schlichting; Structure and Chemistry of Cytochrome P450. Chem. Rev. 2005, 105, 2253-2278, 10.1021/cr0307143.
- Jonathan Rittle; Michael T. Green; Cytochrome P450 Compound I: Capture, Characterization, and C-H Bond Activation Kinetics. Science 2010, 330, 933-937, 10.1126/science.1193478.
- François Ogliaro; Nathan Harris; Shimrit Cohen; Michael Filatov; Samuël P. de Visser; Sason Shaik; A Model “Rebound” Mechanism of Hydroxylation by Cytochrome P450: Stepwise and Effectively Concerted Pathways, and Their Reactivity Patterns. J. Am. Chem. Soc. 2000, 122, 8977-8989, 10.1021/ja991878x.
- Bernard Meunier; Samuël P. de Visser; Sason Shaik; Mechanism of Oxidation Reactions Catalyzed by Cytochrome P450 Enzymes. Chem. Rev. 2004, 104, 3947-3980, 10.1021/cr020443g.