ENZYMES OF POLYAMINE METABOLISM

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 多胺，包括腐胺、亚精胺和精胺，是原核和真核细胞正常生长所必需的。 我们有兴趣研究参与多胺生物合成和降解的一些酶。 这些酶包括S-腺苷甲硫氨酸脱羧酶（S-adenosylmethionine decarboxylase，S-腺苷甲硫氨酸脱羧酶）、S-腺苷甲硫氨酸脱羧酶（S-adenosylmethionine decarboxylase，S-腺苷甲硫氨酸脱羧酶）、S-腺苷甲硫氨酸脱羧酶、精胺氧化酶和S-腺苷甲硫氨酸脱羧酶/SpdSyn融合蛋白。 β-MetDC催化S-腺苷甲硫氨酸（β-Met）脱羧形成S-腺苷甲硫氨酸胺（dcMet）。 此前，Ealick实验室已经解决了Thermotoga maritima，人类和马铃薯的结构。 从布氏锥虫（Trypanosoma brucei（T. brucei）、克氏锥虫Trypanosoma cruzi（T. cruzi）、硕大利什曼原虫（L. major）和巴西利什曼原虫（L. braziliensis）通过形成具有催化失活的调节亚基的异二聚体（称为prozyme）而增强。 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，跳过其他多胺降解酶所需的限制性乙酰基添加到精胺的速率。 这使得它更有效地从细胞中去除精胺，以及产生高水平的反应副产物过氧化氢，这对癌细胞具有细胞毒性。 在嗜热四膜虫中，C3 MetDC与亚精胺合酶（SpdSyn）偶联，其将丙胺基团从脱羧SAM转移到腐胺以产生甲硫腺苷和亚精胺，作为双功能酶。

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.