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

Zsófia Bata, Renzhe Qian, Alexander Roller, Jeannie Horak, László Csaba Bencze, Csaba Paizs, Friedrich Hammerschmidt, B. Vértessy, L. Poppe

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 recognizes 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 as being a 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. (Figure presented.).

Original languageEnglish
Pages (from-to)2109-2120
Number of pages12
JournalAdvanced Synthesis and Catalysis
Volume359
Issue number12
DOIs
Publication statusPublished - Jun 19 2017

Fingerprint

Phenylalanine Ammonia-Lyase
Enantiomers
Phenylalanine
Ammonia
Acids
Amino acids
Aromatic Amino Acids
Enzymes
Carboxylic acids
Ammonia-Lyases
Mirrors
Bearings (structural)
Enzyme kinetics
Herbicides
Calorimetry
Substrates
Prosthetics
Titration
Ligands
phosphonic acid

Keywords

  • amino acids
  • aminophosphonic acids
  • bioinformatics
  • calorimetry
  • enzyme inhibition
  • MIO enzymes

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Cite this

A Methylidene Group in the Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia-Lyases. / Bata, Zsófia; Qian, Renzhe; Roller, Alexander; Horak, Jeannie; Bencze, László Csaba; Paizs, Csaba; Hammerschmidt, Friedrich; Vértessy, B.; Poppe, L.

In: Advanced Synthesis and Catalysis, Vol. 359, No. 12, 19.06.2017, p. 2109-2120.

Research output: Contribution to journalArticle

Bata, Zsófia ; Qian, Renzhe ; Roller, Alexander ; Horak, Jeannie ; Bencze, László Csaba ; Paizs, Csaba ; Hammerschmidt, Friedrich ; Vértessy, B. ; Poppe, L. / A Methylidene Group in the Phosphonic Acid Analogue of Phenylalanine Reverses the Enantiopreference of Binding to Phenylalanine Ammonia-Lyases. In: Advanced Synthesis and Catalysis. 2017 ; Vol. 359, No. 12. pp. 2109-2120.
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