CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I

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。 氨甲酰磷酸合成酶（CPS）是尿素循环的关键酶。 它的作用是捕获氨和碳酸氢盐，并在ATP水解驱动的循环的第一步中产生氨基甲酰磷酸。 其细菌同源物E. Coli CPS II型，采用额外的步骤从谷氨酰胺产生氨，并且具有催化不同反应步骤的三个活性位点，其产物通过100？长的分子内通道转移。 结果表明，牛蛙CPS I型（氨利用型）可以通过双突变转化为CPS II型（谷氨酰胺利用型）。 此外，两种类型的CPS具有不共享同源性并且响应于不同激活剂分子的变构结构域。 为了了解两种类型的CPS之间的差异，我们建议确定来自牛蛙（R.Catesbeiana）及其人类同源物的CPS I型的结构。

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.