Structure-Function Correlations in a Type III Extradiol Dioxygenase

该奖项由化学系的生命过程化学项目和分子和细胞生物学系的分子生物物理组资助佐治亚州立大学的刘爱民博士研究3-羟基邻氨基苯甲酸酯-3，4-双加氧酶(HAO)。这种酶在六元芳环的间位上进行氧化环的裂解，反应称为外加氧合。Hao是建立在Cupin结构折叠(称为III型外加氧双加氧酶)基础上的外加氧合酶的原型成员。本项目的目标是研究底物识别、氧结合、活化、选择性靶向，并鉴定HAO催化反应的中间产物。此外，刘的实验室试图确定该酶的另一个类似Rubredoxin的Fe(Cys)4中心的作用，该中心不是催化所必需的，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外源双加氧酶共有的共同步骤。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，其最终目的是提取能量。刘的实验室研究一种特定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激活及其特定结合到代谢物中的理解。通过使用生化方法、光谱工具、X射线结晶学和计算模型来回答这些科学问题。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较低的群体的成员，参与化学和生物前沿的研究。从研究中获得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.