NOVEL PROSTAGLANDIN SYNTHASE

说明： 人类前列腺素合成酶，环氧合酶-1和-2，是 阿司匹林和其他非类固醇消炎药的靶标。这些 两种酶的序列同源性为65%，它们受到 深入研究它们的结构-功能及其机制 有催化作用和抑制作用。某些珊瑚含有大量的 前列腺素(占干重的2-3%)。在之前赞助的一次非洲摩擦中 合作中，Samel博士确定了 在北极珊瑚中发现了环氧合酶，并在 哺乳动物珊瑚PH合成酶的催化活性 酵素。研究人员现在已经获得了部分cdna克隆。 来自北极和加勒比海珊瑚的珊瑚PG合成酶 含有很高的前列腺素含量。这些DNA含有大约50%的氨基酸 对哺乳动物酶的酸性同一性。在本研究提案中， 研究人员将克隆全长无效的cDNA并表达这些 原核生物和真核生物中的酶。这些酶将是 表征并与哺乳动物的特性进行比较 环氧合酶。预计这一比较将提供有价值的 洞察人类前列腺素合成酶的结构和功能。

DESCRIPTION: The human prostaglandin synthases, cyclooxygenase-1 and -2, are the targets of aspirin and other non-steroidal anti-inflammatory drugs. These two enzymes, which share 65% of sequence identity, are subject to intensive study in terms of their structure-function and their mechanism of catalysis and inhibition. Certain corals contain large amounts of prostaglandins (2-3% of dry weight). In a previous FRICA sponsored collaboration, Dr. Samel identified the biosynthetic pathway of cyclooxygenase in an arctic coral and discovered important differences in the catalytic activities of the coral PH synthase from the mammalian enzymes. The investigators have now obtained the partial cDNA clones of the of the coral PG synthase from the arctic as well as Caribbean corals that contain high prostaglandin contents. These cDNAs show about 50% amino acid identity to the mammalian enzymes. In the present research proposal, the investigators will clone the full length null cDNAs and express these enzymes in prokaryotes as well as in eukaryotes. These enzymes will be characterized and compared to the properties of the mammalian cycloooxygenases. It is expected that a comparison will provide valuable insights into the structure-function of the human prostaglandin synthases.