Modulation of Metalloprotein Activities through Fine-tuning Reduction Potentials

通过微调还原电位调节金属蛋白活性

• 批准号: 2108837
• 负责人: Yi Lu
• 金额: $ 56.1万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108837&HistoricalAwards=false
• 关键词: Modulation; Metalloprotein; Activities; through; Fine

With the support of the Chemistry of Life Processes (CLP) Program in the Chemistry Division, Dr. Yi Lu from the University of Illinois at Urbana-Champaign plans to modulate metalloprotein activities through fine-tuning reduction potentials. In the process, the research will contribute to the fundamental understanding of how to tune reduction potentials and correlate it with functional properties. Many chemical and biological processes involve redox reactions, whose efficiency is largely defined by reduction potentials. In Nature, each metalloprotein covers a certain reduction potential range required for its function. A systematic understanding of common factors that affect the reduction potential of different metalloproteins across the entire range of physiological reduction potentials remains elusive. To address this limitation, the Lu group plans to engineer the protein azurin to vary the reduction potential of the copper site to address the question of how tuning reduction potentials can modulate enzymatic functions, knowledge that would be applicable to many biological and chemical systems. Dr. Lu will integrate research with education through developing lecture and lab modules for undergraduate and graduate courses that incorporate multidisciplinary research results. The PI will focus on recruiting students from groups underrepresented in STEM (science, technology, engineering and mathematics) to participate in the research through outreach activities and on creating and maintaining a diverse, equitable, and inclusive culture to allow the recruits to thrive in learning and research. This project builds on the previous success in Dr. Lu’s lab in tuning the reduction potential of the type 1 copper center in azurin to span a 2 V physiological Eº´ range with minimal perturbation of the primary coordination sphere. It focuses on the engineering secondary coordination sphere interactions, including hydrogen bonding (H-bonding) and hydrophobicity to modulate metalloprotein activities, including (1) the S-nitrosylation reactivity of a Cu site and stepwise nitrosylation of a nonheme Fe site in an engineered azurin, (2) the oxygen reduction activity of the T1Cu center in a small laccase, and (3) changing the reduction potential of an Fe-S cluster incorporated into azurin. The pursuit of these objectives is expected to result in deeper insights into how reduction potentials of metalloproteins can be tuned and how the functions of metalloproteins can be expanded beyond electron transfer. The new knowledge could serve as a strong basis for the design of metalloproteins and metal complexes with predictable reduction potentials that can be used in applications such as solar energy conversion, fuel cells, and small molecule activation.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.

在化学过程的化学过程（CLP）计划的支持下，伊利诺伊大学Urbana-Champaign大学的Yi Lu博士计划通过微调减少潜力来调节金属蛋白活动。在此过程中，该研究将有助于对如何调整减少电位的基本理解并将其与功能特性相关联。许多化学和生物学过程涉及氧化还原反应，其效率在很大程度上取决于降低电位。在自然界中，每种金属蛋白涵盖其功能所需的一定降低势范围。对影响整个物理减少潜力范围内不同金属蛋白减少潜力的共同因素的系统理解仍然难以捉摸。为了应对这一限制，LU组计划设计蛋白质蓝蛋白，以改变铜位点的减少潜力，以解决调整减少电位如何调节酶促功能的问题，这些知识适用于许多生物学和化学系统。 LU博士将通过开发融合多学科研究结果的本科和研究生课程的讲座和实验室模块来将研究与教育整合。 PI将着重于从STEM（科学，技术，工程和数学）中代表性不足的群体中招募学生，以通过外展活动以及创造和维持多样性，公平和包容的文化来参与研究，以使新兵在学习和研究中蓬勃发展。该项目基于Lu博士实验室的先前成功，以调整Azurin中1型铜中心的减少潜力，以跨越2 V的生理Eº´范围，而主要的协调领域的扰动极少。 It focuses on the engineering secondary coordination sphere interactions, including hydrogen bonding (H-bonding) and Hydrophobicity to modulate metalloprotein activities, including (1) the S-nitrosylation reactivity of a Cu site and stepwise nitrosylation of a nonheme Fe site in an engineered azurin, (2) the oxygen reduction activity of the T1Cu center in a small laccase, and (3) changing the将Fe-S簇的降低潜力掺入硫蛋白酶中。预计对这些目标的追求将更深入地了解如何调节金属蛋白的还原电位以及如何扩展金属蛋白的功能超出电子传递。这些新知识可以作为金属蛋白和金属配合物设计具有可预测的还原潜力的强大基础，可以在诸如太阳能转换，燃料电池和小分子激活等应用中使用。这奖反映了NSF的法定任务，并通过使用该基金会的智力功能和广泛的影响来评估NSF的法定任务，并被认为是珍贵的支持。