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

• Type: Article in International Scientific Journal
• Date: 2015

Authors

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

Journal

Title: Archives of Biochemistry and Biophysics

Vol. 582

Pages: 107-115

ISSN: 0003-9861

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 20 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9