Dynamic Properties that Enhance Enzyme Function

描述(申请人提供)：这项研究的长期目标包括开发方法学，以允许询问蛋白质结构的折叠、灵活性和动力学，以及以新颖的方式开发和使用荧光探针，以增强我们对蛋白质结构、动力学和功能的了解。在拟议的五年研究中，重点将通过稳态、稳态前和单分子动力学研究来研究改性DHFRs的机理。荧光光谱将用于研究蛋白质构象的变化及其与DHFR催化关键步骤的关系。 与公众健康相关：本项目的目的是描述和量化特定的序列、结构和动态特性，这些特性可以增强酶的催化作用。拟议的研究将为酶的功能提供重要的见解，并将促进蛋白质设计和药物发现努力。DHFR酶是重要的抗肿瘤和抗微生物药物的靶标，将是我们努力的重点。

DESCRIPTION (provided by applicant): The long term goals of this research include the development of methodology to permit the folding, flexibility and dynamics of protein structure to be interrogated, and the development and use of fluorescent probes in novel ways to enhance our understanding of protein structure, dynamics and function. During the five years of proposed research, the focus of efforts will be on study of the mechanism of modified DHFRs through steady state, pre-steady state and single molecule kinetic studies. Fluorescence spectroscopy will be used to study the protein conformational changes and their association with the key steps in DHFR catalysis. PUBLIC HEALTH RELEVANCE: The present project is aimed at describing and quantifying the particular sequence, structural and dynamic properties that operate to enhance enzymatic catalysis. The proposed studies will provide important insights into enzyme function and will foster protein design and drug discovery efforts. The enzyme DHFR, which is the target of important antineoplastic and antimicrobial drugs, will be the focus of our efforts.