ENZYMES OF POLYAMINE METABOLISM

多胺代谢酶

• 批准号: 8361599
• 负责人: STEVEN E EALICK
• 金额: $ 0.11万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361599
• 关键词: Adenosylmethionine Decarboxylase; Anabolism; Cells; Chimeric Proteins; Coupled; Decarboxylation; Degradation Pathway; Enzymes; Eukaryotic Cell; Excision; Funding; Grant; Human; Hydrogen Peroxide; Laboratories; Leishmania braziliensis; Leishmania major; Metabolism; National Center for Research Resources; Normal Cell; Polyamines; Potato; Principal Investigator; Prokaryotic Cells; Propylamines; Putrescine; Reaction; Research; Research Infrastructure; Resources; S-Adenosylmethionine; Source; Spermidine; Spermidine Synthase; Spermine; Structure; Tetrahymena thermophila; Thermotoga maritima; Trypanosoma brucei brucei; Trypanosoma cruzi; United States National Institutes of Health; cancer cell; cell growth; cost; cytotoxic; interest; polyamine oxidase; structural biology

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 多胺，包括腐霉菌，精子和精子，对于原核细胞和真核细胞的正常细胞生长至关重要。 我们有兴趣研究参与多胺生物合成和降解的许多酶。 这些酶包括S-腺苷甲硫代脱羧酶（AdometDC），AdometDC prozyme，精子氧化酶和AdometDC/SPDSYN的融合蛋白。 ADOMETDC催化S-腺苷硫氨酸（ADOMEM）的脱羧化形成S-腺苷甲氨基胺（DCADOMET）。 以前，Ealick实验室已经解决了Thermotoga Maritima，Human和Mota AdometDC的结构。 AdometDC的催化活性来自Brucei（T。Brucei），Cruzi锥虫（T. Cruzi），L。Major（L. Major）和Braziliensis（L. braziliensis），通过与近亲级别的反向进行近距离抗衡的形成，可以增强BRAZILIENSIS（L. Braziliensis）（L. braziliensis）。 精子氧化酶是一种诱导酶，是多胺降解途径的一部分。它直接将精子分解为精子，跳过了其他多胺降解酶所需的乙酰基的速率限制添加的乙酰基。 这使其在从细胞中去除精子以及产生高水平的反应副产物过氧化氧化物（对癌细胞具有细胞毒性）的效率更高。 在嗜热四膜虫中，AdometDC与精子合酶（SPDSYN）结合，将丙酰胺基团从脱羧的SAM转移到putrescine中，以产生甲基硫代腺苷和精子，作为双分支酶。