Mechanism of the tyrosine ammonia lyase reaction-tandem nucleophilic and electrophilic enhancement by a proton transfer

Chemistry : a European Journal
Sarolta PilbákL Poppe

Abstract

Quantum mechanics/molecular mechanics calculations in tyrosine ammonia lyase (TAL) ruled out the hypothetical Friedel-Crafts (FC) route for ammonia elimination from L-tyrosine due to the high energy of FC intermediates. The calculated pathway from the zwitterionic L-tyrosine-binding state (0.0 kcal  mol(-1)) to the product-binding state ((E)-coumarate+H(2)N-MIO; -24.0 kcal  mol(-1); MIO = 3,5-dihydro-5-methylidene-4H-imidazol-4-one) involves an intermediate (IS, -19.9 kcal  mol(-1)), which has a covalent bond between the N atom of the substrate and MIO, as well as two transition states (TS1 and TS2). TS1 (14.4 kcal  mol(-1)) corresponds to a proton transfer from the substrate to the N1 atom of MIO by Tyr300-OH. Thus, a tandem nucleophilic activation of the substrate and electrophilic activation of MIO happens. TS2 (5.2 kcal  mol(-1)) indicates a concerted C-N bond breaking of the N-MIO intermediate and deprotonation of the pro-S β position by Tyr60. Calculations elucidate the role of enzymic bases (Tyr60 and Tyr300) and other catalytically relevant residues (Asn203, Arg303, and Asn333, Asn435), which are fully conserved in the amino acid sequences and in 3D structures of all known MIO-containing ammonia lyases and 2,3-aminomuta...Continue Reading

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Citations

Mar 17, 2015·Archives of Biochemistry and Biophysics·Gaspar P PintoNino Russo
Apr 6, 2013·Current Opinion in Chemical Biology·Matthew M HeberlingDick B Janssen
Apr 14, 2017·Organic & Biomolecular Chemistry·László Csaba BenczeCsaba Paizs
May 13, 2017·Chemical Reviews·Fabio ParmeggianiNicholas J Turner
May 7, 2014·Physical Chemistry Chemical Physics : PCCP·Qianqian HouYongjun Liu
Aug 1, 2015·Angewandte Chemie·Eduardo BustoWolfgang Kroutil
Nov 5, 2019·Trends in Plant Science·Jaime Barros, Richard A Dixon

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