Reaction Specificity in Pyridoxal Phosphate Enzymes

化学部的生命化学过程计划为该奖项提供资金。加州大学戴维斯分校的Michael Toney教授研究维生素B6依赖的酶。酶催化生命系统的化学反应，极大地提高反应速度。一大类代谢重要的酶使用维生素B6(吡哆醛磷酸)来催化反应以利用氮。作为一类，这些酶还具有合成和商业化生产高价值化学品(如除草剂)的良好潜力。这项研究的目的是了解依赖维生素B6的酶特定生产某些化学物质的基础。为了实现这一目标，对维生素B6的改变版本的研究和实验室酶的进化正在进行中。这笔资金有助于本科生和研究生的专业发展，并允许开发一门本科课程，重点是为未被充分代表的少数族裔本科生为实验室研究做准备。磷酸吡哆醛(又称PLP或维生素B6)依赖的酶是所有生物体氮代谢的中心。作为一个基团，它们催化十几种不同的反应类型，每种反应类型具有多种底物特异性。到目前为止，已经鉴定了大约230种不同的PLP酶活性。人们普遍了解用于催化这些不同反应的基本有机化学，但不了解实现底物和反应专一性的机制。这项研究有两个主要部分：第一个部分使用辅酶类似物来确定辅酶亲电性对反应特异性的影响，第二个部分涉及实验室重建祖先的非特异性酶，并通过最少数量的关键突变重演它们到今天的酶的进化。这些研究有助于确定磷酸吡哆醛依赖酶反应专一性的电子和结构决定因素。这笔资金还有助于本科生和研究生的专业发展，并允许开发一门本科课程，重点是为未被充分代表的少数族裔本科生为实验室研究做准备。

The Chemistry of Life Processes Program in the Chemistry Division funds this award. Professor Michael Toney of the University of California-Davis investigates vitamin B6 dependent enzymes. Enzymes catalyze the chemical reactions of living systems, enhancing the rates of reaction by enormous amounts. A large class of metabolically-important enzymes use vitamin B6 (pyridoxal phosphate) to catalyze reactions for nitrogen utilization. As a class, these enzymes also have excellent potential for the synthesis and commercial production of high-value chemicals (such as herbicides). The goal of this research is to understand the basis for the specific production of certain chemicals by vitamin B6 dependent enzymes. To achieve this goal, a combination of studies on altered versions of vitamin B6, and laboratory enzyme evolution is underway. This funding contributes to the professional development of undergraduate and graduate students, and allows the development of an undergraduate course focused on preparing under-represented minority undergraduate students for laboratory research. Pyridoxal phosphate (also called PLP or vitamin B6) dependent enzymes are central to nitrogen metabolism in all organisms. As a group, they catalyze more than a dozen different reaction types, with each reaction type having multiple substrate specificities. Approximately 230 different PLP enzyme activities have been identified to date. The fundamental organic chemistry used to catalyze these different reactions is generally understood, but the mechanisms by which substrate and reaction specificity are achieved are not. This research has two major components: the first employs coenzyme analogues to determine the influence of coenzyme electrophilicity on reaction specificity, and the second involves laboratory reconstruction of ancestral, non-specific enzymes and recapitulation of their evolution to present day enzymes via a minimal number of critical mutations. These studies help to define the electronic and structural determinants of reaction specificity in pyridoxal phosphate dependent enzymes. This funding also contributes to professional development of undergraduate and graduate students, and allows for the development of an undergraduate course focused on preparing under-represented minority undergraduate students for laboratory research.