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
基本信息
- 批准号:2201279
- 负责人:
- 金额:$ 56.1万
- 依托单位:
- 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:2021-11-15 至 2024-09-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
在化学系生命过程化学(CLP)项目的支持下,伊利诺伊大学香槟分校的Yi Lu博士计划通过微调还原电位来调节金属蛋白的活性。在此过程中,该研究将有助于从根本上理解如何调节还原电位并将其与功能性质相关联。许多化学和生物过程涉及氧化还原反应,其效率在很大程度上由还原电位决定。在自然界中,每种金属蛋白都覆盖了其功能所需的一定还原电位范围。一个系统的理解,影响不同的金属蛋白在整个范围内的生理还原电位的还原电位的共同因素仍然难以捉摸。为了解决这一限制,Lu团队计划对蛋白质天青蛋白进行工程改造,以改变铜位点的还原电位,从而解决调节还原电位如何调节酶功能的问题,这些知识将适用于许多生物和化学系统。卢博士将通过为本科生和研究生课程开发讲座和实验室模块,将多学科的研究成果与教育相结合。PI将专注于从STEM(科学,技术,工程和数学)代表性不足的群体中招募学生,通过外联活动参与研究,并创造和维护多元化,公平和包容性的文化,使新兵在学习和研究中茁壮成长。该项目建立在Lu博士实验室先前成功调整天青蛋白中1型铜中心的还原电位的基础上,以最小的主配位圈扰动跨越2 V生理Eº´范围。 它侧重于工程次级配位相互作用,包括氢键(H-键合)和疏水性来调节金属蛋白活性,包括(1)工程化天青蛋白中Cu位点的S-亚硝基化反应性和非血红素Fe位点的逐步亚硝基化,(2)小漆酶中T1 Cu中心的氧还原活性,以及(3)改变掺入天青蛋白的Fe-S簇的还原电位。这些目标的追求,预计将导致更深入的了解如何金属蛋白的还原电位可以调整和金属蛋白的功能可以扩展到电子转移之外。新的知识可以作为一个强有力的基础,为金属蛋白质和金属络合物的设计,可预测的还原电位,可用于应用,如太阳能转换,燃料电池,和小分子活化。这个奖项反映了NSF的法定使命,并已被认为是值得的支持,通过评估使用基金会的智力价值和更广泛的影响审查标准。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Structural Basis for the Effects of Phenylalanine on Tuning the Reduction Potential of Type 1 Copper in Azurin
- DOI:10.1021/acs.inorgchem.3c01365
- 发表时间:2023-07-10
- 期刊:
- 影响因子:4.6
- 作者:Liu,Yiwei;Marshall,Nicholas M.;Lu,Yi
- 通讯作者:Lu,Yi
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Yi Lu其他文献
Silica coating with well-defined micro-nano hierarchy for universal and stable surface superhydrophobicity
具有明确微纳米层次结构的二氧化硅涂层,具有通用且稳定的表面超疏水性
- DOI:
10.1016/j.cplett.2019.06.001 - 发表时间:
2019-09 - 期刊:
- 影响因子:2.8
- 作者:
Huan Liu;Wei Geng;Cheng-Jing Jin;Si-Ming Wu;Yi Lu;Jie Hu;Hao-Zheng Yu;Gang-Gang Chang;Tian Zhao;Ying Wan;Zhi-Qiang Luo;Ge Tian;Xiao-Yu Yang - 通讯作者:
Xiao-Yu Yang
Retraction: CXCR6 Induces Prostate Cancer Progression by the AKT/Mammalian Target of Rapamycin Signaling Pathway.
撤回:CXCR6 通过雷帕霉素信号通路的 AKT/哺乳动物靶标诱导前列腺癌进展。
- DOI:
10.1158/0008-5472.can-22-2399 - 发表时间:
2022 - 期刊:
- 影响因子:11.2
- 作者:
Jianhua Wang;Yi Lu;Jingcheng Wang;A. Koch;Jian Zhang;R. Taichman - 通讯作者:
R. Taichman
Prevention of oxaliplatin-related neurotoxicity by ω-3 PUFAs
ω-3 PUFA 预防奥沙利铂相关的神经毒性
- DOI:
- 发表时间:
2020 - 期刊:
- 影响因子:1.6
- 作者:
Xinjie Zhang;Haitao Chen;Yi Lu;Chao Xu;Wang Yao;Lu Xu;Runzhe Zhang;Liping Zhang;Qinghua Yao - 通讯作者:
Qinghua Yao
Practical Considerations for Using RNA Sequencing in Management of B-Lymphoblastic Leukemia: Ma-Spore ALL-Seq 2020 Implementation Strategy.
使用 RNA 测序管理 B 淋巴细胞白血病的实际注意事项:Ma-Spore ALL-Seq 2020 实施策略。
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:4.1
- 作者:
Winnie H. Ni Chin;Zhenhua Li;Nan Jiang;E. Lim;J. Y. Suang Lim;Yi Lu;Kean;Shirley Kow Yin Kham;Bernice L. Zhi Oh;A. Tan;H. Ariffin;Jun J. Yang;Allen Eng - 通讯作者:
Allen Eng
Electrodeposition of porous Sn-Ni-Cu alloy anode for lithium-ion batteries from nickel matte in deep eutectic solvents
低共熔溶剂中镍冰铜电沉积锂离子电池多孔 Sn-Ni-Cu 合金阳极
- DOI:
10.1149/2.0881910jes - 发表时间:
2019 - 期刊:
- 影响因子:3.9
- 作者:
Shuaichao Rao;Xingli Zou;Shujuan Wang;Tianyu Shi;Yi Lu;Li Ji;Hsien-Yi Hsu;Qian Xu;Xionggang Lu - 通讯作者:
Xionggang Lu
Yi Lu的其他文献
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{{ truncateString('Yi Lu', 18)}}的其他基金
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 - 财政年份:2021
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
Deeper Understanding of Factors that Fine-tune Redox Potentials of Metalloproteins
更深入地了解微调金属蛋白氧化还原电位的因素
- 批准号:
2201259 - 财政年份:2021
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
RAPID: Developing a novel biosensor for rapid, direct and selective detection of COVID-19 using DNA aptamer-nanopore
RAPID:开发一种新型生物传感器,利用 DNA 适体纳米孔快速、直接和选择性检测 COVID-19
- 批准号:
2029215 - 财政年份:2020
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
Deeper Understanding of Factors that Fine-tune Redox Potentials of Metalloproteins
更深入地了解微调金属蛋白氧化还原电位的因素
- 批准号:
1710241 - 财政年份:2017
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
Tuning Redox Potentials of Metal Centers in a Single Protein
调节单一蛋白质中金属中心的氧化还原电位
- 批准号:
1413328 - 财政年份:2014
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
CAREER: Scheduling and Resource Allocation in the Cloud using Graphical Models and Randomized Algorithms
职业:使用图形模型和随机算法在云中进行调度和资源分配
- 批准号:
1150080 - 财政年份:2012
- 资助金额:
$ 56.1万 - 项目类别:
Continuing Grant
Research Initiation Award Grant: Advancing Bioinformatics through Services Computing
研究启动奖:通过服务计算推进生物信息学
- 批准号:
1137555 - 财政年份:2011
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
A Biosynthetic Approach toward Biomimetic Studies of Metalloproteins Involved in Long-range Electron Transfer
参与长程电子转移的金属蛋白仿生研究的生物合成方法
- 批准号:
1058959 - 财政年份:2011
- 资助金额:
$ 56.1万 - 项目类别:
Continuing Grant
I-Corps: Portable sensors using the widely available personal glucose monitor
I-Corps:使用广泛使用的个人血糖监测仪的便携式传感器
- 批准号:
1158781 - 财政年份:2011
- 资助金额:
$ 56.1万 - 项目类别:
Standard Grant
A Biosynthetic Approach Toward Biomimetic Studies of Metalloproteins Involved in Long-range Electron Transfer
参与长程电子转移的金属蛋白仿生研究的生物合成方法
- 批准号:
0552008 - 财政年份:2006
- 资助金额:
$ 56.1万 - 项目类别:
Continuing Grant
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