REAL

Methylidene Group in Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia-Lyases

Bata, Zsófia and Qian, Renzhe and Roller, Alexander and Horak, Jeannie and Bencze, László Csaba and Paizs, Csaba and G. Vértessy, Beáta and Poppe, László (2017) Methylidene Group in Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia-Lyases. ADVANCED SYNTHESIS & CATALYSIS, 359. pp. 2109-2120. ISSN 1615-4150

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Abstract

Aromatic amino acid ammonia-lyases and aromatic amino acid 2,3-aminomutases contain the post-translationally formed prosthetic 3,5-dihydro-4-methylidene-5H-imidazol-5-one (MIO) group. MIO-enzymes catalyze the stereoselective synthesis of α- or β-amino acid enantiomers, making these chemical processes environmentally friendly and affordable. Characterization of novel inhibitors enables structural understanding of enzyme mechanism and recognize promising herbicide candidates as well. The present study found, that both enantiomers of the aminophosphonic acid analogue of the natural substrate phenylalanine and a novel derivative bearing a methylidene at the β-position inhibited phenylalanine ammonia-lyases (PAL), representing MIO enzymes. X-ray methods unambiguously determined the absolute configuration of all tested enantiomers during their synthesis. Enzyme kinetic measurements revealed the enantiomer of the methylidene substituted substrate analogue being mirror image relation to the natural L-phenylalanine as the strongest inhibitor. Isothermal titration calorimetry (ITC) confirmed the binding constants and provided a detailed analysis of the thermodynamic driving forces of ligand binding. Molecular docking suggested that binding of the (R)- and (S)-enantiomers is possible by a mirror image packing.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 27 Feb 2018 15:21
Last Modified: 27 Feb 2018 15:21
URI: http://real.mtak.hu/id/eprint/75167

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