Structure-Function Correlations in a Type III Extradiol Dioxygenase

通过该奖项，化学学部生命过程化学项目和分子与细胞生物学学部分子生物物理集群将资助乔治亚州立大学的刘爱民博士对3-羟基苯甲酸-3,4-双加氧酶（HAO）进行表征。这种酶在六元芳香环的中间位置进行氧化环切割，这一反应被称为外二醇双氧化。HAO是建立在杯状结构褶皱上的外二醇双加氧酶的原型成员（称为III型外二醇双加氧酶）。本课题的目标是研究底物识别、氧结合、活化、选择性靶向，并鉴定由HAO催化的反应的中间体。此外，Liu实验室试图确定酶的另一个类似红霉素的Fe(Cys)4中心的作用，它不是催化所必需的，但在细菌酶中是保守的。本研究旨在为了解这些酶的机制和外二醇双加氧酶的共同步骤建立一个框架。铁结合的氧化中间体的化学、结构和光谱特性将有助于阐明铁依赖的氧活化和氧化机制。分子氧与有机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酶完成这一任务的机制。实验室创造的知识促进了对氧活化及其与代谢物的特定结合的理解。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科学问题。这种多学科的追求为理科生创造了大量的机会，包括在科学领域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。

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.