title: Kinetic analysis of the inhibition of phenylalanine ammonia-lyase by 2-aminoindan-2-phosphonic acid and other phenylalanine analogues.
abstract: The conformationally restricted phenylalanine analogue 2-aminoindan-2-phosphonic acid (AIP) inhibits phenylalanine ammonia-lyase (PAL) competitively in a time-dependent manner. This phenomenon was investigated in more detail with the heterologously expressed, highly purified homotetrameric PAL-1 isozyme from parsley. The kinetic analysis revealed that the enzyme-inhibitor complex is formed in a single "slow" step with an association rate of k(2)=2.6+/-0.04 10(4) M(-1) s(-1). The inhibition is reversible with a dissociation rate of k(-2)=1.8+/-0.04 10(-4) s(-1) and an equilibrium constant of K(i)=7+/-2 nM. The previously described PAL inhibitor (S)-2-aminooxy-3-phenylpropanoic acid [(S)-AOPP] was also found to be a slow-binding inhibitor of PAL-1. The carboxyl analogue of AIP, 2-aminoindan-2-carboxylic acid, served as a substrate of PAL-1 and was converted to indene-2-carboxylic acid.
authors.affiliation: Institute of Plant Sciences, Federal Institute of Technology Zürich, CH- 8092 Zürich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Appert
authors.forename: Jerzy
authors.initials: J
authors.lastname: Zoń
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Amrhein
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007189:Indans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D028528:Petroselinum / Q000201:enzymology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010650:Phenylalanine Ammonia-Lyase / Q000037:antagonists & inhibitors*
chemical_list: C411146:2-aminoindan-2-phosphonic acid; D004791:Enzyme Inhibitors; D007189:Indans; D007527:Isoenzymes; D063065:Organophosphonates; D010649:Phenylalanine; D010650:Phenylalanine Ammonia-Lyase