ENZYMES OF POLYAMINE METABOLISM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 多胺，包括腐胺、亚精胺和精胺，对于原核和真核细胞的正常生长都是必不可少的。我们感兴趣的是研究与多胺生物合成和降解有关的一些酶。这些酶包括S-腺苷蛋氨酸脱羧酶(ADO-MetDC)、ADO-MetDC酶、精胺氧化酶以及ADO-MetDC/SpdSyn融合蛋白。 ADOMetDC催化S-腺苷甲硫氨酸(ADOMet)脱羧生成S-腺苷甲硫胺(DcADOMet)。此前，Ealick实验室已经解决了Thermotoga maritima、人类和土豆Adobe MetDC的结构。布氏锥虫、克鲁兹锥虫、大利什曼原虫和巴西利什曼原虫的ADOMetDC的催化活性通过形成具有催化不活跃的调节亚基的杂二聚体而得到增强。精胺氧化酶是一种诱导性酶，是多胺降解途径的一部分；它直接将精胺分解为亚精胺，跳过了其他多胺降解酶所需的乙酰基对精胺的限速加成。这使得它在从细胞中去除精胺以及产生高水平的反应副产物过氧化氢方面更加有效，过氧化氢对癌细胞具有细胞毒性。在嗜热四膜虫中，ADOMetDC与精胺合成酶(SpdSyn)偶联，SpdSyn作为双功能酶将丙胺基团从脱羧基SAM转移到腐胺生成甲硫腺苷和亚精胺。

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.