title: Chemistry and diversity of pyridoxal-5'-phosphate dependent enzymes.
abstract: Pyridoxal-5'-phosphate (PLP) is a versatile cofactor that enzymes use to catalyze a wide variety of reactions of amino acids, including transamination, decarboxylation, racemization, β- and γ-eliminations and substitutions, retro-aldol and Claisen reactions. These reactions depend on the ability of PLP to stabilize, to a varying degree, α-carbanionic intermediates. Furthermore, oxidative decarboxylations and rearrangements suggest that PLP can stabilize radical intermediates as well. The reaction mechanisms of two PLP-dependent enzymes are discussed, kynureninase and tyrosine phenol-lyase (TPL). Kynureninase catalyzes a retro-Claisen reaction of kynurenine to give anthranilate and alanine. The key step, hydration of the γ-carbonyl, is assisted by acid-base catalysis with the phosphate of the PLP, mediated by a conserved tyrosine, and an oxyanion hole. TPL catalyzes the reversible elimination of phenol, a poor leaving group, from l-tyrosine. In TPL, the Cβ-Cγ bond cleavage is accelerated by ground state strain from the bending of the substrate ring out of the plane with the Cβ-Cγ bond. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.
authors.affiliation: Department of Chemistry, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA. Electronic address: plp@uga.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Phillips
mesh_terms: D002384:Catalysis; D006867:Hydrolases / Q000737:chemistry*; D011732:Pyridoxal Phosphate / Q000502:physiology*; D014447:Tyrosine Phenol-Lyase / Q000737:chemistry*
chemical_list: D011732:Pyridoxal Phosphate; D006867:Hydrolases; C021480:kynureninase; D014447:Tyrosine Phenol-Lyase
keywords: Acid–base catalysis; Pyridoxal-5′-phosphate; Reaction mechanism; Steady-state kinetics; Stopped-flow kinetics; Substrate strain