Catalytic Mechanism of Pyruvate−Formate Lyase Revisited

摘要: The catalytic mechanism of the glycyl-radical-containing enzyme pyruvate-formate lyase (PFL) is investigated using high-level quantum chemical methods. PFL catalyzes reversible conversion pyruvate and coenzyme A (CoA) into formate acetylated CoA. Large models are employed, based on a recent X-ray crystal structure in complex with substrate. rate-limiting step shown to be homolytic C1-C2 bond cleavage pyruvate, which occurs after attack Cys418 radical carbonyl carbon pyruvate. For acetylation CoA, we propose new mechanism, released formyl anion abstracts hydrogen atom directly from This way, acetyl group transfer becomes facile. full potential energy curve for reactions presented.