Pyruvate formate lyase: A new perspective

• Tipo: Artigo em Revista Científica Internacional
• Data: 2003

Autores

Lucas, MD (Autor) Outra; Fernandes, PA (Autor) FCUP; Eriksson, LA (Autor) Outra; Ramos, MJ (Autor) FCUP

Revista

Título: Journal of Physical Chemistry B

Vol. 107

Páginas: 5751-5757

ISSN: 1520-6106

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 14 Citações

Scopus - 11 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7