CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.