The role of conformationally plastic loops in enzyme function, stability and regulation

基于蛋白质的催化剂，被称为酶，是地球上所有生命所必需的。因此，了解酶如何进行它们介导的化学转化是基本了解生命的关键。此外，改变或改造酶功能的能力将为生物技术开辟新的途径，如开发新型生物燃料和生产治疗感染和疾病的新药。为了使这些想法成为现实，我们对酶如何作为有效和选择性的生物催化剂发挥作用有一个深入和基本的了解是至关重要的。朝着这个目标，最近的研究表明，酶是灵活的分子，并存在于溶液中的相互转换的构象状态的人口，这些构象波动是至关重要的适当的酶功能。既然这种现象已经被确定，我们的目标是了解酶的这种构象灵活性如何与酶正确发挥功能的能力联系在一起。为了帮助发展这种了解构象的灵活性如何影响酶的功能，我们将调查的作用，酶的灵活性在家庭的酶被确定为磷酸烯醇式丙酮酸羧激酶。通过这项研究计划，我们将开发一个更好的图片如何在环元件的构象转变，是酶的结构的一部分，催化功能，酶的稳定性和活性的调节是必要的，以及调查移动的元素的蛋白质结构的结构限制，通过分析酶在这个家庭从不同的物种。

Protein based catalysts, known as enzymes, are essential to all life on earth. It follows that understanding how enzymes carry out the chemical transformations they mediate is key to a basic understanding of life. In addition, the ability to alter or engineer enzyme function will open up new avenues in biotechnology such as the development of novel biofuels and the generation of new pharmaceuticals to treat infection and disease. For these ideas to become a reality it is of paramount importance that we have an intimate and fundamental understanding of how enzymes function as efficient and selective biological catalysts. Working towards this goal, recent studies have demonstrated that enzymes are flexible molecules and exist in solution as a population of interconverting conformational states and that these conformational fluctuations are vitally important to proper enzyme function. Now that this phenomenon has been identified, it is our goal to understand how this conformational flexibility of enzymes is tied to the ability of the enzyme to function correctly. To help develop this understanding of how conformational flexibility impacts enzyme function, we will investigate the role of enzyme flexibility in the family of enzymes identified as phosphoenolpyruvate carboxykinases. Through this program of research, we will develop a better picture of how conformational transitions in loop elements that are part of the enzyme's structure are necessary for catalytic function, enzyme stability, and regulation of activity as well as investigate the structural constraints on mobile elements of protein structure through analysis of enzymes in this family from diverse species.