STRUCTURE AND FUNCTION OF EXTRADIOL DIOXYGENASES

微生物中三种胞外二醇双加氧酶的结构 有害芳香族化合物的降解将在原子 通过X射线晶体学的分辨率。 的配合物的结构 还将测定具有底物和抑制剂的酶。 的 结构信息将被分析相对于生化 这些酶和相关酶的功能。 这一行动的直接目标是 项目包括具体说明结构决定因素， 底物结合和催化。 Extradiol双加氧酶是一类非血红素Fe（II）依赖性酶， 在芳香族化合物的催化剂中发挥关键作用， 它们催化芳环裂解的能力。 的途径 几种关键代谢物的合成和降解，包括氨基 核酸，维生素和激素，需要双加氧酶催化 开环反应 Extradiol双加氧酶也与 参与许多天然和合成的微生物降解 芳香族化合物 靶向酶催化微生物中芳环的裂解， 降解联苯、二苯并二恶英、二苯并呋喃及其 氯化类似物。 这组基板包括多个 重大健康风险。 该项目是一个合作努力的一部分，其目标包括 通过二醇外双加氧酶的环裂解机制的阐明， 阐明这些酶的不可逆抑制机制， 氯代代谢物，以及开发微生物系统， 提高了降解各种有害芳香族化合物的能力， 氯代芳香族污染物。

The structures of three extradiol dioxygenases involved in the microbial degradation of detrimental aromatic compounds will be determined at atomic resolution by X-ray crystallography. Structures of complexes of the enzymes with substrates and inhibitors also will be determined. The structural information will be analyzed with respect to the biochemical functions of these and related enzymes. The immediate goals of this project include the specification of the structural determinants of substrate binding and catalysis. Extradiol dioxygenases are a class of nonheme,Fe(II)-dependent enzymes that play critical roles in the catabolism of aromatic compounds by virtue of their ability to catalyze the cleavage of aromatic rings. Pathways for the synthesis and degradation of several key metabolites, including amino acids, nucleic acids, vitamins, and hormones, require dioxygenase-catalyzed ring cleavage reactions. Extradiol dioxygenases also are intimately involved in the microbial degradation of many natural and synthetic aromatic compounds. The targeted enzymes catalyze the cleavage of aromatic rings in microbial pathways that degrade biphenyl, dibenzo-p-dioxin, dibenzofuran and their chlorinated analogs. This group of substrates includes a number of significant health risks. This project is part of a collaborative effort whose goals include elucidation of the mechanism of ring cleavage by extradiol dioxygenases, elucidation of the mechanism of irreversible inhibition of these enzymes by chlorinated metabolites, and development of microbial systems with an increased ability to degrade a broad range of detrimental aromatic and chloroaromatic pollutants.