ENZYMES OF POLYAMINE BIOSYNTHESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 腐胺、亚精胺和精胺对细胞的生长和分化很重要，存在于所有形式的生命中。在快速增殖的癌细胞和肿瘤细胞中发现多胺水平升高，调节多胺的生物合成和分解代谢机制是癌症治疗的一种有前途的工具。S-腺苷蛋氨酸脱羧酶(ADO-MetDC)是一种丙酮基依赖的脱羧酶，是多胺生物合成途径中的关键酶。这种酶的抑制剂有可能成为抗癌药物。ADOMetDC催化S-腺苷蛋氨酸(ADOMet)生成脱羧基S-腺苷蛋氨酸(DcADOMet)，其丙胺基团转移为腐胺和亚精胺，分别生成亚精胺和亚精胺。一旦脱羧基，dcADOMet就致力于多胺途径。该项目的主要目标是获得Adobe MetDC和带有新抑制剂的关键突变体的晶体结构，以确定它们的结合构象和它们与酶的关键相互作用。这些结构信息将有助于设计与酶产生良好相互作用的抑制剂，从而成为更有效的Adobe MetDC抑制剂。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The polyamines putrescine, spermidine and spermine are important for cell growth and differentiation and are found in all forms of life. Elevated levels of the polyamines are found in rapidly proliferating cancerous and tumor cells and regulating the polyamine biosynthetic and the catabolic machinery is a promising tool for cancer therapy. S-Adenosylmethionine Decarboxylase (AdoMetDC) is a pyruvyl dependent decarboxylase and a critical enzyme in the polyamine biosynthetic pathway. The inhibitors to this enzyme have the potential to be anti-cancer drugs. AdoMetDC catalyses the conversion of S-Adenosylmethionine (AdoMet) to decarboxylated S-Adenosylmethionine (dcAdoMet) and the propylamine group of dcAdoMet is transferred to putrescine and spermidine to form spermidine and spermine respectively. Once decarboxylated, dcAdoMet is committed to the polyamine pathway. The primary goal of the project is to obtain crystal structures of AdoMetDC and key mutants with new inhibitors to determine their binding conformations and the key interactions they make to the enzyme. The structural information will help in the design of inhibitors which make favourable interactions with the enzyme and hence be more potent inhibitors of AdoMetDC.