EVOLUTIONARY RELATIONSHIPS AMONG NAD-GLYCOHYDROLASES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在所有形式的生命中都观察到了裂解烟酰胺-核糖键的酶。特别令人感兴趣的是ADP核糖基转移酶(ARTS)。这组酶首先被确定为导致霍乱、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，序列分析证实它们与细菌毒素在进化上是相关的。在这项研究中，我们建议研究其他ART和NAD糖水解酶(NADase)之间的关系，以了解它们的进化关系和细胞功能。我们建议确定是否存在其他生物的艺术，包括植物、真菌和无脊椎动物。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-核糖键的酶的进化关系。这项提议的目的是确定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。由此，我们将更好地理解和理解ART在脊椎动物中的作用。

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.