Mechanism of dioxygen activation in 2-oxoglutarate-dependent enzymes: a hybrid DFT study.
The reaction mechanism for dioxygen activation in 2-oxoglutarate-dependent enzymes has been studied by means of hybrid density functional theory. The results reported here support a mechanism in which all chemical transformations take place on a quintet potential-energy surface. More specifically, the activated dioxygen species attacks the carbonyl group of the co-substrate producing the Fe(II)-persuccinate-CO(2) complex, which readily releases the carbon dioxide molecule. The step in which the Fe(II)-peracid-CO(2) complex is formed is found to be rate-limiting and irreversible. Subsequent heterolysis of the Obond;O bond in the Fe(II)-persuccinate complex proceeds in two one-electron steps and produces the high-valent iron-oxo species Fe(IV)dbond;O, which is most likely to be responsible for oxidative reactions catalyzed by 2-oxoglutarate-dependent enzymes. The concerted pathway for simultaneous Obond;O and Cbond;C bond cleavage on the septet potential-energy surface is found to be less favorable. The relative stability of different forms of the active iron-oxo species is assessed, and the quintet five-coordinate complex is found to be most stable.
Borowski
Tomasz
T
Department of Physics, Stockholm Center for Physics, Astronomy and Biotechnology, Stockholm University, 106 91 Stockholm, Sweden. borowski@physto.se
Bassan
Arianna
A
Siegbahn
Per E M
PE
D001665:Binding Sites; D002384:Catalysis; D004789:Enzyme Activation; D006418:Heme / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000737:chemistry*; D008432:Mathematical Computing; D010100:Oxygen / Q000378:metabolism*; D010105:Oxygenases / Q000737:chemistry* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D007656:Ketoglutaric Acids; D017382:Reactive Oxygen Species; D006418:Heme; D010105:Oxygenases; D010100:Oxygen