CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I

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。 氨基甲酰磷酸合成酶(CPS)I型是尿素循环的关键酶。它的作用是捕获氨和碳酸氢盐，并在由三磷酸腺苷水解驱动的循环的第一步产生氨基甲酰磷酸。其已知结构的细菌同系物E.Coli CPS Type II额外使用了一个步骤来从谷氨酰胺生成氨，并有三个催化不同步骤反应的活性部位，其产物通过100°长的分子内通道进行转移。结果表明，牛蛙CPS I型(氨利用型)可通过双突变转化为CPS II型(谷氨酰胺利用型)。此外，两种类型的CP都有变构结构域，它们没有同源性，对不同的激活剂分子有反应。为了了解两种类型的CPS之间的差异，我们建议确定卡特斯贝纳(牛蛙)及其人类同源物的CPS I型结构。

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. Carbamoyl phosphate synthetase (CPS) type I is a key enzyme of urea cycle. Its role is to capture ammonia and bicarbonate and produce carbamoyl phosphate in the first step of the cycle driven by ATP hydrolysis. Its bacterial homologue with known structure, E. Coli CPS type II, employs an extra step to produce ammonia from glutamine and has three active sites catalyzing different steps of reaction, products of which are transferred over 100 ¿ long intramolecular channels. It was shown that bullfrog CPS type I (ammonia-utilizing) can be converted to CPS type II (glutamine-utilizing) by double mutation. In addition, two types of CPS have allosteric domains which share no homology and respond to different activator molecules. To understand the differences between two types of CPS we propose to determine the structure of CPS type I from R.Catesbeiana (bullfrog) and its human homologue.