Structure-Function Correlations in a Type III Extradiol Dioxygenase

III 型外二醇双加氧酶的结构-功能相关性

• 批准号: 1309942
• 负责人: Aimin Liu
• 金额: $ 45万
• 依托单位: Georgia State University Research Foundation, Inc.
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309942&HistoricalAwards=false
• 关键词: Structure; Function; Correlations; Type; III

With this award, the Chemistry of Life Processes Program in the Chemistry Division and the Molecular Biophysics Cluster in the Molecular and Cellular Biology Division are funding Dr. Aimin Liu from Georgia State University to characterize 3-hydroxyanthranilate-3,4-dioxygenase (HAO). This enzyme performs oxidative ring-cleavage at the meta position of six-membered aromatic rings in a reaction known as extradiol dioxygenation. HAO is a prototypic member of extradiol dioxygenases built upon a cupin structural fold (known as type III extradiol dioxygenases). The goal of this project is to study the substrate recognition, oxygen binding, activation, selective targeting, and to identify the intermediates of the reactions catalyzed by HAO. Furthermore, the Liu lab seeks to identify the role of an additional rubredoxin-like Fe(Cys)4 center of the enzyme, which is not required for catalysis but is conserved in bacterial enzymes. The research aims to build a framework for understanding the mechanism of these enzymes and common steps shared by extradiol dioxygenases. The chemical, structural, and spectroscopic properties of iron-bound oxygenated intermediates will help illuminate iron-dependent oxygen activation and oxidation mechanisms. The incorporation of molecular oxygen into organic molecules is one of the most important metabolic processes in nature and its ultimate purpose is energy extraction. The Liu laboratory studies the mechanism by which a particular enzyme accomplishes this task. Knowledge created by the lab advances the understanding of oxygen activation and its specific incorporation into metabolites. The scientific questions are answered by using biochemical methods, spectroscopic tools, X-ray crystallography, and computational modeling. This multidisciplinary pursuit creates substantial opportunities to engage science students, including members of groups underrepresented in science, in research at the frontier of chemistry and biology. The knowledge gleaned from the research are incorporated in the biochemistry and bioinorganic chemistry curriculum.

有了这个奖项，化学部的生命过程化学项目和分子与细胞生物学部的分子生物物理学集群正在资助来自格鲁吉亚州立大学的Aimin Liu博士，以表征3-羟基邻氨基苯甲酸-3，4-双加氧酶（HAO）。这种酶在称为二醇外双氧化的反应中在六元芳环的Meta位进行氧化环裂解。HAO是建立在cupin结构折叠上的外二醇双加氧酶（称为III型外二醇双加氧酶）的原型成员。本项目的目标是研究HAO催化反应的底物识别、氧结合、活化、选择性靶向以及中间体的鉴定。此外，Liu实验室试图确定酶的额外rubredoxin样Fe（Cys）4中心的作用，该中心不是催化所需的，但在细菌酶中是保守的。这项研究旨在建立一个框架，以了解这些酶的机制和共同的步骤所共享的extradiol双加氧酶。铁结合的含氧中间体的化学，结构和光谱性质将有助于阐明铁依赖的氧活化和氧化机制。分子氧与有机物分子的结合是自然界中最重要的代谢过程之一，其最终目的是能量的提取。Liu实验室研究了一种特殊的酶完成这一任务的机制。 该实验室创造的知识促进了对氧活化及其特异性结合到代谢物中的理解。这些科学问题可以通过使用生化方法、光谱工具、X射线晶体学和计算建模来回答。这种多学科的追求创造了大量的机会，让理科学生，包括在科学中代表性不足的群体的成员，在化学和生物学的前沿研究。从研究中收集的知识被纳入生物化学和生物无机化学课程。