STRUCTURE AND FUNCTION OF EXTRADIOL DIOXYGENASES

与微生物有关的三种外源双加氧酶的结构 有害芳香族化合物的降解将在原子上进行测定 X-射线结晶学的分辨率。的络合物的结构 带有底物和抑制剂的酶也将被测定。这个 关于生化的结构信息将被分析 这些酶和相关酶的功能。这样做的直接目标是 项目包括对结构决定因素的规范 底物结合和催化。 胞外双加氧酶是一类非血红素、铁(II)依赖的酶 在芳香族化合物的分解代谢中发挥关键作用 它们催化芳香环断裂的能力。的路径 几种关键代谢物的合成和降解，包括氨基 酸、核酸、维生素和激素都需要双加氧酶催化。 环断裂反应。外源性双加氧酶也与 参与微生物降解的许多天然和合成的 芳香化合物。 靶向酶催化微生物中芳香环的裂解 联苯、二苯并-对二恶英、二苯并呋喃及其降解途径 氯化类似物。这组衬底包括多个 严重的健康风险。 该项目是合作努力的一部分，其目标包括 阐明外源性双加氧酶裂环的机理， 对这些酶不可逆抑制机制的阐明 氯代谢物和微生物系统的发展 提高了降解多种有害芳香族和 氯代芳烃污染物。

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.