Reaction Specificity in Pyridoxal Phosphate Enzymes

化学部的生命过程化学项目为该奖项提供资金。加州大学戴维斯分校的Michael Toney教授研究了维生素B6依赖酶。酶催化生命系统的化学反应，极大地提高反应速率。 一大类代谢重要的酶使用维生素B6（磷酸吡哆醛）催化氮利用反应。作为一类，这些酶也具有合成和商业生产高价值化学品（如除草剂）的巨大潜力。这项研究的目的是了解维生素B6依赖酶特定生产某些化学物质的基础。为了实现这一目标，正在进行一项关于改变维生素B6版本和实验室酶进化的研究。这笔资金有助于本科生和研究生的专业发展，并允许开发本科课程，重点是为代表性不足的少数民族本科生进行实验室研究做好准备。磷酸吡哆醛（也称为PLP或维生素B6）依赖酶是所有生物体氮代谢的中心。作为一个组，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。迄今为止，已经鉴定了大约230种不同的PLP酶活性。用于催化这些不同反应的基本有机化学通常被理解，但实现底物和反应特异性的机制却不被理解。这项研究有两个主要组成部分：第一个采用辅酶类似物来确定辅酶亲电性对反应特异性的影响，第二个涉及祖先的非特异性酶的实验室重建，并通过最少数量的关键突变重演它们进化到今天的酶。这些研究有助于确定磷酸吡哆醛依赖酶反应特异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，并允许开发本科课程，重点是为代表性不足的少数民族本科生进行实验室研究做好准备。

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.