Determining the role of dynamics in allosteric communication and function for BLVRB

确定动力学在 BLVRB 变构通讯和功能中的作用

• 批准号: 1807326
• 负责人: Elan Eisenmesser
• 金额: $ 45万
• 依托单位: University of Colorado at Denver-Downtown Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807326&HistoricalAwards=false
• 关键词: Determining; role; dynamics; allosteric; communication

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Elan Eisenmesser from the University of Colorado Denver to investigate how motions within an enzyme communicate to control enzyme function. With the development of technological methods capable of identifying the positions of all the atoms in molecules over the last two decades, it has become increasingly clear that macromolecules, and particularly enzymes, are reliant on a range of motions for their functions. However, how these motions are communicated across an enzyme in order to control their functions is less understood. Utilizing newly developed techniques that bridge molecular biology and nuclear magnetic resonance, graduate and undergraduate students will reveal how motions on multiple timescales communicate within a critical biological enzyme, called Bilirubin Reductase B, and whether there is cross-talk between movements on different timescales. Such studies could impact efforts to engineer enzymes by considering both their structure and intrinsic motions. Dr. Eisenmesser also plans to introduce these studies to minority undergraduates in order to train students in molecular biology and state-of-the-art biophysical techniques that probe the atomic level details of both structure and motions.The research project is aimed at elucidating how networks of coupled motions regulate active site dynamics and how these in turn modulate catalytic turnover. Dynamic communication is now well understood to play critical roles in enzyme function and many recent studies have shown that motions are only partially correlated. Thus, identifying the molecular basis of these partial couplings and specifically modulating distal dynamics in order to control enzyme function will significantly impact efforts for enzyme engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学司的化学过程计划正在为科罗拉多大学丹佛大学的Elan Eisenmesser博士提供资金，以调查酶内部的动作如何进行控制以控制酶功能。随着技术方法的发展，能够识别过去二十年来所有原子的位置，越来越清楚的是，大分子，尤其是酶，尤其是酶，依赖于一系列功能的动作。但是，为了控制其功能，如何在酶上传达这些动作。 利用新开发的技术桥接分子生物学和核磁共振，研究生和本科生将揭示多个时间尺度上的运动在关键的生物学酶（称为胆红素还原酶b）中如何进行交流，以及在不同时间刻度上运动之间是否有互相关。这样的研究可能会通过考虑其结构和内在动作来影响促进酶的努力。 Eisenmesser博士还计划将这些研究引入少数群体本科生，以培训学生的分子生物学和最先进的生物物理技术，以探测结构和动作的原子水平细节。该研究旨在阐明如何阐明如何阐明耦合运动的网络调节主动位点动力学以及这些网络又如何调节催化转换。 现在，人们对动态通信在酶功能中起着关键作用，并且许多最近的研究表明，运动仅部分相关。 因此，确定这些部分耦合的分子基础，并专门调节远端动态以控制酶功能，将对酶工程的努力产生重大影响。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识绩效和智力优点和评估的支持值得的。更广泛的影响审查标准。