Pyruvate formate lyase: A new perspective

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Lucas, MD (Author) Other; Fernandes, PA (Author) FCUP; Eriksson, LA (Author) Other; Ramos, MJ (Author) FCUP

Journal

Title: Journal of Physical Chemistry B

Vol. 107

Pages: 5751-5757

ISSN: 1520-6106

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 11 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-000-G8R

DOI: 10.1021/jp0223096

Abstract (EN): The enzymatic conversion of pyruvate into formate by the radical enzyme pyruvate formate lyase is studied using density functional theory with the hybrid B3LYP functional. The residues glycine 734, cysteine 418, and cysteine 419 are known to be fundamental for the reaction to occur. We here represent G734(.) by CHO-NH-CH.-CO-NH2, which allows for an efficient pi delocalization, whereas the two neighboring cysteines are modeled using methylthiol or as a larger complex that includes part of the protein backbone. The latter representation permits a differentiation of the two cysteines and provides an explanation of the catalytic role of the enzyme. Previous theoretical studies of the mechanism have employed a neutral model to represent pyruvate. In the present work, we have used negatively charged model, which leads to modifications of the behavior of the enzyme. Based on the obtained results, a four-step mechanism is proposed, in which the reaction is initiated by H transfer from C418 via C419 to the glycyl radical. The C418 thiyl radical adds pyruvate from which the formyl radical is detached via a quasi-planar transition state. The previously postulated tetrahedral intermediate does not exist according to the present models. The formyl radical then abstracts a hydrogen atom from C419, forming the formate anion.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7