ENZYMES OF POLYAMINE METABOLISM

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 多胺，包括腐胺、亚精胺和精胺，对于原核和真核细胞的正常细胞生长都是必需的。 我们有兴趣研究许多参与多胺生物合成和降解的酶。 这些酶包括 S-腺苷甲硫氨酸脱羧酶 (AdoMetDC)、AdoMetDC 原酶、精胺氧化酶和 AdoMetDC/SpdSyn 融合蛋白。 AdoMetDC 催化 S-腺苷甲硫氨酸 (AdoMet) 脱羧形成 S-腺苷甲硫胺 (dcAdoMet)。 此前，Ealick实验室已经解析了海栖热袍菌、人类和马铃薯AdoMetDC的结构。 来自布氏锥虫 (T. brucei)、克氏锥虫 (T. cruzi)、硕大利什曼原虫 (L. Major) 和巴西利什曼原虫 (L. braziliensis) 的 AdoMetDC 的催化活性通过形成具有催化失活调节亚基（称为原酶）的异二聚体而得到增强。 精胺氧化酶是一种诱导酶，是多胺降解途径的一部分；它将精胺直接分解为亚精胺，跳过了其他多胺降解酶所需的向精胺添加乙酰基的限速过程。 这使得它能够更有效地从细胞中去除精胺，并产生高水平的反应副产物过氧化氢，过氧化氢对癌细胞具有细胞毒性。 在嗜热四膜虫中，AdoMetDC 与亚精胺合酶 (SpdSyn) 偶联，后者将丙胺基团从脱羧 SAM 转移到腐胺，生成甲硫腺苷和亚精胺，作为一种双功能酶。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Polyamines, including putrescine, spermidine, and spermine, are essential for normal cell growth in both prokaryotic and eukaryotic cells. We are interested in studying a number of enzymes involved in polyamine biosynthesis and degradation. These enzymes include S-adenosylmethionine decarboxylase (AdoMetDC), the AdoMetDC prozyme, spermine oxidase, and the fusion protein of AdoMetDC/SpdSyn. AdoMetDC catalyzes the decarboxylation of S-adenosylmethionine (AdoMet) to form S-adenosylmethioninamine (dcAdoMet). Previously, the Ealick laboratory has solved the structure of Thermotoga maritima, human, and potato AdoMetDC. The catalytic activity of AdoMetDC from Trypanosoma brucei (T. brucei), Trypanosoma cruzi (T. cruzi), Leishmania major (L. major), and Leishmania braziliensis (L. braziliensis) is enhanced by the formation of a heterodimer with a catalytically inactive regulatory subunit, termed the prozyme. Spermine oxidase is an inducible enzyme that is part of the polyamine degradation pathway; it breaks down spermine directly to spermidine, skipping the rate limiting addition of an acetyl group to spermine that other polyamine degradation enzymes require. This makes it much more efficient in the removal of spermine from cells, as well as producing high levels of the reaction byproduct hydrogen peroxide, which is cytotoxic to cancer cells. In Tetrahymena thermophila, AdoMetDC is coupled with spermidine synthase (SpdSyn), which transfers the propylamine group from decarboxylated SAM to putrescine to generate methythioadenosine and spermidine, as a bifunctional enzyme.