STRUCTURES AND MECHANISMS OF COPPER AMINE OXIDASES

含铜胺氧化酶广泛分布于自然界和 参与生物源伯胺的新陈代谢。胺 氧化物酶在心血管中可能具有多种功能， 哺乳动物的胃肠道和神经系统。胺氧化酶是 也负责结缔组织结构的交联性 蛋白质(弹性蛋白和胶原蛋白)。似乎有许多化合物 具有抗真菌、抗原虫或抗癌活性 胺氧化酶；例如，五烷双胺，一种治疗 艾滋病患者卡氏肺孢子虫肺炎的治疗 属于一类抑制胺氧化酶的化合物。这个 主要目标是确定多个胺的三维结构 氧化酶，包括至少一种人类酶，并阐明 胺氧化和辅因子(TPQ)生物发生的机制。在……里面 此外，相关酶半乳糖的结构和生物合成 氧化物酶，将被检测。定点突变，光谱学， 采用了动力学测量和结晶学方法。水晶 两个胺氧化酶的结构已被解析，揭示了几个 新颖的特征，包括第二个金属结合位点。组合 结构和机械数据WI允许详细了解 这些重要酶的结构和功能有待开发。

Copper-containing amine oxidases are widely distributed in nature and are involved in the metabolism of biogenic primary amines. Amine oxidases may have a variety of functions in the cardiovascular, gastrointestinal, and nervous systems of mammals. Amine oxidases are also responsible for the cross-linking of connective tissue structural proteins (elastin and collagen). It appears that numerous compounds with antifungal; antiprotozoal, or anticancer activities may target amine oxidases; for example pentamidine,a leading drug for the treatment of Pneumocystis carinii pneumonia (PCP) in AIDS patients belongs to class of compounds that inhibit amine oxidases. The principal goals are to determine the 3-D structures of multiple amine oxidases, including at least one human enzyme, and to elucidate the mechanisms of amine oxidation and cofactor (TPQ) biogenesis. In addition, the structure and biosynthesis of a related enzyme, galactose oxidase, will be examined. Site-directed mutagenesis, spectroscopy, kinetics measurements, and crystallography are employed. The crystal structures of two amine oxidases have been solved, revealing several novel features, including a second metal-binding site. Combining structural and mechanistic data WI permit a detailed understanding of the structure and function of these important enzymes to be developed.