EVOLUTIONARY RELATIONSHIPS AMONG NAD-GLYCOHYDROLASES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在所有的生命形式中都可以观察到裂解烟酰胺-核糖基键的酶。 特别感兴趣的是ADP核糖基转移酶（ART）。 这组酶首先被鉴定为引起霍乱、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ARTs，序列分析证实它们与细菌毒素在进化上相关。 在这项研究中，我们建议调查其他ART和NAD-糖水解酶（NAD酶）的进化关系和细胞功能之间的关系。 我们建议从其他生物体，包括植物，真菌和无脊椎动物中确定是否存在ART。 我们还将确定其他NAD酶的序列，并分析它们与其他裂解烟酰胺-核糖基键的酶的进化关系。 该建议的重点是确定ARTs作为脊椎动物调节系统的起源以及致病毒素如何重塑为对维持生命重要的系统。 从这一点我们将更好地了解ARTs在脊椎动物中的功能。

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.