Investigating the structure, function, and regulation of polyamine acetyltransferases

研究多胺乙酰转移酶的结构、功能和调节

• 批准号: 9982363
• 负责人: Misty Kuhn
• 金额: $ 38.75万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982363
• 关键词: Acetyltransferase; Affect; Bacteria; Bacterial Physiology; Biological Process; Cell physiology; Enzymes; Eukaryota; Evolution; Foundations; Future; Goals; Knowledge; Microbial Biofilms; Pathogenesis; Pathogenicity; Play; Polyamines; Process; Property; Regulation; Research; Research Project Grants; Role; Spermidine; Spermine; Structure; Therapeutic; Treatment Efficacy; Virulence; Work; insight; norspermidine; pathogenic bacteria; targeted treatment

PROJECT SUMMARY The proposed research seeks to study the functions and regulation of bacterial polyamine acetyltransferases (PAATs). These enzymes belong to the large Gcn5-related N-acetyltransferase (GNAT) superfamily, and acetylate a variety of polyamines including spermine, spermidine, and norspermidine. The main function associated with bacterial PAATs has been to maintain intracellular polyamine concentrations; however, increasing evidence has shown that PAATs likely play a larger role in bacterial physiology and pathogenesis than previously anticipated. While PAATs have been well-studied in eukaryotes, there is a significant gap in knowledge regarding bacterial PAAT identities, functions and regulation. Additionally, there is a limited understanding of how allosteric effectors and oligomerization regulate PAAT function, and how these properties effect PAAT roles in bacterial biofilms and other cellular processes. Since polyamines have been implicated in bacterial virulence and pathogenesis, knowledge about PAAT regulation is critical for developing effective therapeutics toward bacterial pathogens. Therefore, the goal of the proposed research is to determine the roles of PAATs and how they are regulated across pathogenic and non-pathogenic bacteria. We will investigate the following key questions over the next five years: 1) Which bacterial GNATs are PAATs?, 2) How are bacterial PAATs regulated?, and 3) How do bacterial PAATs regulate cellular processes?. The answers to these questions will yield insight into PAAT evolution and distribution across bacteria, identify strategies for targeted therapeutics, and add to the fundamental knowledge of PAAT function and regulatory properties in bacteria.

项目摘要 拟议的研究旨在研究细菌多胺乙酰转移酶的功能和调节 （Paats）。这些酶属于与GCN5相关的大型N-乙酰基转移酶（GNAT）超家族，并且 乙酰酸酯多种多胺，包括精子，精子和氯丁胺。主要功能 与细菌PAAT相关的是维持细胞内多胺浓度。然而， 越来越多的证据表明，PAAT可能在细菌生理和发病机理中起更大的作用 比以前预期的。虽然真核生物在真核生物中进行了充分研究，但存在很大的差距 有关细菌PAAT身份，功能和调节的知识。此外，还有一个有限的 了解变构效应子和低聚如何调节PAAT功能以及这些特性如何 在细菌生物膜和其他细胞过程中影响PAAT的作用。由于多胺与 细菌毒力和发病机理，关于PAAT调节的知识对于发展有效至关重要 针对细菌病原体的治疗剂。因此，拟议的研究的目的是确定角色 PAAT及其在致病性和非致病细菌中的调节。我们将调查 在接下来的五年中以下关键问题：1）哪些细菌gn是Paats？，2）细菌如何 PAAT受调节？和3）细菌PAAT如何调节细胞过程？这些问题的答案 将洞悉对细菌的PAAT进化和分布，确定靶向治疗剂的策略， 并增加了细菌中PAAT功能和调节特性的基本知识。