Catalytic mechanism of pyruvate-formate lyase revisited

被引:12
作者
Guo, JD [1 ]
Himo, F [1 ]
机构
[1] ALBANOVA, Royal Inst Technol, Dept Biotechnol, SE-10691 Stockholm, Sweden
关键词
D O I
10.1021/jp0478054
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
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 the reversible conversion of pyruvate and coenzyme A (CoA) into formate and acetylated CoA. Large models are employed, based on a recent X-ray crystal structure of PFL in complex with the pyruvate substrate. The rate-limiting step is shown to be the homolytic C1-C2 bond cleavage of pyruvate, which occurs after the attack of the Cys418 radical on the carbonyl carbon of pyruvate. For the acetylation of CoA, we propose a new mechanism, in which the released formyl radical anion abstracts a hydrogen atom directly from CoA. This way, the acetyl group transfer from Cys418 becomes facile. The full potential energy curve for the PFL reactions is presented.
引用
收藏
页码:15347 / 15354
页数:8
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