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

Archives of Biochemistry and Biophysics
Gaspar P PintoNino Russo

Abstract

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 kcat 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 corre...Continue Reading

Citations

Jul 29, 2015·Archives of Biochemistry and Biophysics·V Moliner
Jul 14, 2016·Applied Microbiology and Biotechnology·Yao LuMingliang Jin
May 13, 2017·Chemical Reviews·Fabio ParmeggianiNicholas J Turner
Mar 9, 2019·Organic & Biomolecular Chemistry·Jonathan W Bogart, Albert A Bowers
Oct 5, 2017·Chemistry : a European Journal·Pedro FerreiraMaria João Ramos
Jun 9, 2018·Applied Biochemistry and Biotechnology·Longbao ZhuZhemin Zhou
Nov 5, 2019·Trends in Plant Science·Jaime Barros, Richard A Dixon

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