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
• 负责人: Yi Lu
• 金额: --
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2011-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0552008&HistoricalAwards=false
• 关键词: Biosynthetic; Approach; Toward; Biomimetic; Studies

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports research by Professor Yi Lu and the University of Illinois at Urbana-Champaign to gain a deeper understanding of the coordination chemistry and biological role of electron transfer (ET) at metal ion centers such as CuA and [Fe2S2] in proteins by applying two new techniques from biology, i.e. expressed protein ligation (EPL) and loop-directed mutagenesis (LDM). Unnatural amino acids will be introduced by EPL in order to make isostructural substitutions that will make it possible to elucidate the roles of the residues in the primary and secondary coordination sphere of the CuA center in azurin more precisely in determining a) geometric structures, such as the Cu-Cu bond distance and the "diamond core" angle; b) electronic structure, such as the extent of electron delocalization and c) functional properties, such as the reduction potentials and electron transfer rates of the center. LDM will be used to place three prominent ET centers (blue copper, CuA and [Fe2S2] centers) in the same protein framework of azurin, allowing a direct comparison of their structural and functional properties, such as extent of electron delocalization and ET efficiency. Insights obtained from the study will allow the design of metal-binding sites with tunable redox and electron-transfer properties, which is important to biological respiration (in the case of cytochrome oxidase) and the global nitrogen cycle (in the case of N2O-reductase). Introducing two new techniques from biology also allows the advancement of basic coordination chemistry. Lecture and lab modules (including quizzes) will be developed to integrate multidisciplinary research into graduate and undergraduate course instruction. A course called "Chemistry and Biology of Everyday Life" will be enhanced using materials from this research. To broaden participation of underrepresented groups, the PI will give seminars at institutions and summer camps, and participate in summer research opportunity programs.

该奖项在无机，生物有机和有机金属化学计划中支持Yi Lu教授和Urbana-Champaign的伊利诺伊大学伊利诺伊大学的研究，以更深入地了解电子在Cua和[Fe2S2]中的Electer Ion Center在METAIL ION CENTER上的电子转移（ET）的配位化学和生物学作用，从（EPL）和循环指导的诱变（LDM）。 EPL将引入不自然的氨基酸，以使等值替代品将使CuA中心在Azurin中更精确地确定A）几何结构（例如Cu-Cu-cu键距离距离和diaondone core''角度，使CuA中心在Azurin中的主要和次要配位领域的作用成为可能。 b）电子结构，例如电子定位和c）功能特性，例如中心的降低电位和电子传递速率。 LDM将用于将三个突出的ET中心（蓝色铜，CUA和[FE2S2]中心）放在硫蛋白的相同蛋白质框架中，从而可以直接比较其结构和功能性能，例如电子定位和效率的范围。从研究中获得的见解将允许设计具有可调氧化还原和电子转移特性的金属结合位点，这对于生物学呼吸（在细胞色素氧化酶的情况下）和全球氮循环（对于N2O-还原酶）很重要。 引入生物学的两种新技术也可以提高基本协调化学。 将开发讲座和实验室模块（包括测验），以将多学科研究集成到研究生和本科课程教学中。 这项研究的材料将增强称为“日常生活的化学和生物学”课程。为了扩大代表性不足的团体的参与，PI将在机构和夏令营举行研讨会，并参加夏季研究机会计划。