New insights in the catalytic mechanism of tyrosine ammonia-lyase given by QM/MM and QM cluster models

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Gaspar P Pinto (Autor) Outra; Antonio J M Ribeiro (Autor) Outra; Maria J Ramos (Autor) FCUP; Pedro A Fernandes (Autor) FCUP; Marirosa Toscano (Autor) Outra; Nino Russo (Autor) Outra

Revista

Título: Archives of Biochemistry and Biophysics

Vol. 582

Páginas: 107-115

ISSN: 0003-9861

Editora: Elsevier

Indexação

ISI Web of Knowledge - 12 Citações

Scopus - 0 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Ciências biológicas

Outras Informações

ID Authenticus: P-00G-JK6

DOI: 10.1016/j.abb.2015.03.002

Abstract (EN): Tyrosine ammonia lyase (TAL) catalyzes the deamination of tyrosine to p-coumaric acid in purple phototropic bacteria and Actinomycetales. The enzyme is used in bioengineering and has the potential to be used industrially. It belongs to a family of enzymes that uses a 4-methylidene-imidazole-5-one (MIO) cofactor to catalyze the deamination amino acids. In the present work, we used a QM/MM and a QM cluster models of TAL to explore two putative reaction paths for its catalytic mechanism. Part of the N-MIO mechanism was previously studied by computational methods. We improved on previous studies by using a larger, more complete model of the enzyme, and by describing the complete reaction path. The activation energy for this mechanism, in agreement with the previous study, is 28.5 kcal/mol. We also found another reaction path that has overall better kinetics and reaches the products in a single reaction step. The barrier for this Single-Step mechanism is 16.6 kcal/mol, which agrees very well with the experimental kat of 16.0 kcal/mol. The geometrical parameters obtained for the cluster and QM/ MM models are very similar, despite differences in the relative energies. This means that both approaches are capable of describing the correct catalytic path of TAL.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9