Phillips Robert S
Department of Chemistry, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Biochim Biophys Acta. 2015 Sep;1854(9):1167-74. doi: 10.1016/j.bbapap.2014.12.028. Epub 2015 Jan 20.
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.
磷酸吡哆醛（PLP）是一种多功能辅因子，酶利用它催化氨基酸的多种反应，包括转氨作用、脱羧作用、消旋作用、β-和γ-消除及取代反应、逆羟醛缩合反应和克莱森反应。这些反应取决于PLP在不同程度上稳定α-碳负离子中间体的能力。此外，氧化脱羧反应和重排反应表明PLP也能稳定自由基中间体。本文讨论了两种依赖PLP的酶的反应机制，即犬尿氨酸酶和酪氨酸酚裂解酶（TPL）。犬尿氨酸酶催化犬尿氨酸的逆克莱森反应，生成邻氨基苯甲酸和丙氨酸。关键步骤是γ-羰基的水合作用，由PLP的磷酸基团进行酸碱催化，由一个保守的酪氨酸和一个氧负离子洞介导。TPL催化从L-酪氨酸中可逆地消除酚（一种较差的离去基团）。在TPL中，由于底物环与Cβ-Cγ键弯曲而偏离平面产生的基态应变加速了Cβ-Cγ键的断裂。本文是名为：依赖辅因子的蛋白质：进化、化学多样性和生物应用的特刊的一部分。
