EVOLUTIONARY RELATIONSHIPS AMONG NAD-GLYCOHYDROLASES

NAD-糖水解酶之间的进化关系

• 批准号: 7601829
• 负责人: NORMAN J OPPENHEIMER
• 金额: $ 0.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601829
• 关键词: Bacterial Toxins; Cell physiology; Cells; Cholera; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Diphtheria; Enzymes; Funding; Glycoside Hydrolases; Grant; Human; Institution; Invertebrates; Life; Maintenance; Meleagris gallopavo; Mus; NAD+ Nucleosidase; Niacinamide; Object Attachment; Organism; Pertussis; Rattus; Research; Research Personnel; Resources; Sequence Analysis; Source; Surface; Symptoms; System; Toxin; Turkey bird; United States National Institutes of Health; Vertebrates; insight; interest; plant fungi

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. Enzymes that cleave the nicotinamide-ribosyl bond have been observed in all forms of life. Of particular interest is the ADPRibosyltransferases (ARTs). This group of enzymes was first identified as bacterial toxins responsible for the symptoms of cholera, pertussis and diphtheria. More recently ARTs were identified on the surface of vertebrate cells from mice, rats, turkeys and humans, and sequence analysis established them to be evolutionarily related to the bacterial toxins. In this study we propose to investigate the relationship among other ARTs and NAD-glycohydrolases (NADases) as to their evolutionary relationship and cellular function. We propose to establish the presense or absence of ARTs from other organisms including plants, fungi, and invertebrates. We will also determine the sequences of other NADases and analyze their evolutionary relationship with other enzymes that cleave the nicotinamide-ribosyl bond. The foucs of this proposal is to determine the origin of the ARTs as a regulatory system in vertebrates and how a pathogenic toxin can be remolded into a system important to the maintenance of life. From this insight we will better undertand the functions of ARTs in vertebrates.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在所有生命形式中都观察到了裂解烟酰胺-核糖基键的酶。 特别令人感兴趣的是 ADP 核糖基转移酶 (ART)。 这组酶首先被鉴定为导致霍乱、百日咳和白喉症状的细菌毒素。 最近，在小鼠、大鼠、火鸡和人类的脊椎动物细胞表面发现了 ART，序列分析证实它们在进化上与细菌毒素相关。 在这项研究中，我们打算研究其他 ART 和 NAD 糖水解酶 (NADase) 之间的进化关系和细胞功能之间的关系。 我们建议确定其他生物体（包括植物、真菌和无脊椎动物）是否存在 ART。 我们还将确定其他 NADase 的序列，并分析它们与其他裂解烟酰胺-核糖基键的酶的进化关系。 该提案的重点是确定 ART 作为脊椎动物调节系统的起源，以及如何将致病毒素重塑为对维持生命重要的系统。 通过这一见解，我们将更好地了解 ART 在脊椎动物中的功能。