Differentiating the Two Complementary Flavins in a Bifurcating Electron Transfer Flavoprotein

区分二叉电子转移黄素蛋白中的两种互补黄素

• 批准号: 2108134
• 负责人: Anne-Frances Miller
• 金额: $ 45.89万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108134&HistoricalAwards=false
• 关键词: Differentiating; Two; Complementary; Flavins; Bifurcating

With support from the Chemistry of Life Processes Program in the Division of Chemistry, Professor Anne-Frances Miller and her team at the University of Kentucky are examining how bacteria have managed to optimize their energy efficiency. Science has advanced to the point that it is now possible to supply all the energy needed by mankind, from wind and sunlight. However, these are intermittent, low-density sources that need to be 'stepped up' to power appliances such as hair driers. It turns out that bacteria possess enzymes capable of producing concentrated power from readily available fuel sources. These enzymes employ a mechanism wherein pairs of electrons are obtained from a cheap abundant fuel, but only one of the electrons is allowed to run 'down-hill'. The enzyme somehow harnesses this favorable process to drive an unfavorable 'up-hill' reaction that yields a much more potent electron carrier than the starting one. To enable design of materials able to do the same, the proposed research seeks to learn how nature does this. Flavin molecules related to the vitamin riboflavin, bound in proteins as cofactors are central to the mechanism. The planned research seeks to elucidate how the protein adjusts the flavin's reactivity. Flavins are yellow and fall into the larger chemical category of pigments. The broader impact of this work will be to develop a course for non-chemists that will employ fiber art and dyeing activities to explain core chemical concepts. This hands-on learning approach is designed to reach audiences who do not find book- and lecture-based courses compelling. Thus, the proposed work aims to engage a larger audience in the fun and curiosity of chemistry, and to harness chemistry in larger service to society.This research seeks to learn how bifurcating electron transfer flavoproteins (ETFs) tune the reactivities of their two flavins to cause one flavin to execute single electron transfers only, but the other flavin to have a very high energy semiquinone state that causes transfer of one electron to be tightly coupled to transfer of the second. A specific hypothesis is that the pyrophosphate group built into flavin adenine dinucleotide (FAD) could have agency in modulating the activity of the flavin. The proposed work also addresses the nature and lessons inherent in a novel state of the ETF that is proposed to involve cooperation of both flavins. The research integrates computational, spectroscopic, electrochemical, and biochemical strategies. To develop computational approaches and enable interpretation of flavin optical spectra in terms of underlying electronic structure and reactivity, a systematic approach is proposed, beginning with covalently modified flavins. Once validated, computational approaches would then be employed to infer the electronic perturbations produced by different protein sites in which flavins are bound. While flavin spectroscopy is at the center of the proposed research, the proposal exploits pigments more generally as vehicles to make core concepts of chemistry accessible to non-scientist audiences. A lab and lecture course on plant pigments in fiber arts will be developed into a modular on-line course, including guidance for hands-on activities. The team will assemble execution kits that rural schools or homeschoolers will be able to borrow, in order to follow along with recorded demonstrations and presentations. This approach seeks to overcome barriers that prevent many people from engaging with chemistry.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.

在化学过程中的化学过程中的支持下，肯塔基大学的安妮·弗朗西斯·米勒（Anne-Frances Miller）教授和她的团队正在研究细菌如何设法优化其能源效率。 科学已经发展到现在可以从风和阳光下提供人类所需的所有能量。但是，这些是间歇性的低密度来源，需要“加强”到诸如脱毛机等电器上。事实证明，细菌具有能够从易于使用的燃料来源产生浓缩功率的酶。这些酶采用一种机制，其中从便宜的燃料中获得了一对电子，但是只有一种电子被允许运行“下坡”。酶以某种方式利用了这一有利的过程来驱动不利的“上间”反应，该反应产生了比起始载体更有效的电子载体。为了使能够做同样的材料设计，拟议的研究试图了解自然的做法。与维生素核黄素相关的黄素分子在蛋白质中结合，因为辅助因子是该机制的核心。计划的研究旨在阐明蛋白质如何调节黄素的反应性。黄素是黄色的，属于较大的化学颜料类别。这项工作的更广泛的影响是为非化学家开发一门课程，这些课程将采用纤维艺术和染色活动来解释核心化学概念。这种动手学习方法旨在吸引那些找不到基于书籍和讲座的课程引人注目的观众。因此，拟议的工作旨在吸引更大的观众参与化学的乐趣和好奇心，并利用化学对社会的更大服务。这项研究试图如何学习如何将电子传递的电子传递黄油蛋白（ETF）调节，使他们的两种黄素的反应性使一个火文的一种单一的能量仅使单个电子传输能够使单个电子转移，但要执行一个较高的电气转移，这是一个非常高的电气转移，而又有一流的素食，却是一定的，却是一流的，而不是含有较高的电气转移，这是一位果仁的含量。紧密耦合到第二个转移。一个特定的假设是，内置在黄素腺嘌呤二核苷酸（FAD）中的焦磷酸基团可以使代理商调节黄素的活性。拟议的工作还解决了ETF新颖状态固有的本质和教训，该状态涉及两种黄素的合作。该研究集成了计算，光谱，电化学和生化策略。为了开发计算方法并能够根据基础电子结构和反应性来解释黄素光谱，提出了一种系统的方法，从共价修改的黄素开始。一旦经过验证，将采用计算方法来推断黄素绑定的不同蛋白质位点产生的电子扰动。尽管黄素光谱是拟议研究的核心，但该提案更普遍地利用了颜料，因为车辆使非科学主义受众可以使用化学的核心概念。关于纤维艺术中植物色素的实验室和讲座课程将发展为模块化的在线课程，包括动手活动的指导。 该团队将组装执行套件，即农村学校或家庭学生将能够借用，以便进行记录的示威和演示文稿。这种方法旨在克服障碍，以防止许多人参与化学。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来评估值得支持的。