CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I

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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.