STRUCTURES AND MECHANISMS OF COPPER AMINE OXIDASES

含铜胺氧化酶广泛分布于自然界， 参与生物伯胺的代谢。胺 氧化酶在心血管中可具有多种功能， 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 蛋白质（弹性蛋白和胶原蛋白）。似乎许多化合物 具有抗真菌、抗原生动物或抗癌活性， 胺氧化酶;例如喷他脒，一种主要的药物， 艾滋病合并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。的 主要目标是确定多胺的三维结构 氧化酶，包括至少一种人酶，并阐明 胺氧化和辅因子（TPQ）的生物合成机制。在 此外，结构和生物合成的相关酶，半乳糖 氧化酶，将被检查。 定点突变，光谱学， 动力学测量和结晶学。晶体 两种胺氧化酶的结构已经解决，揭示了几个 新特征，包括第二金属结合位点。结合 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.