Catalytic mechanism of pyruvate-formate lyase revisited
2004 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 108, no 39, 15347-15354 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2004. Vol. 108, no 39, 15347-15354 p.
density-functional thermochemistry, exchange, hypophosphite, cleavage
IdentifiersURN: urn:nbn:se:kth:diva-23753DOI: 10.1021/jp0478054ISI: 000224070200077ScopusID: 2-s2.0-6344286013OAI: oai:DiVA.org:kth-23753DiVA: diva2:342452
QC 20100525 QC 201109162010-08-102010-08-102011-09-16Bibliographically approved