Role of Cys-1327 and Cys-1337 in redox sensitivity and allosteric monitoring in human carbamoyl phosphate synthetase.

ABSTRACT: Human carbamoyl phosphate synthetase (hCPS) has evolved critical features that allow it to remove excess and potentially neurotoxic ammonia via the urea cycle, including use of only free ammonia as a nitrogen donor, a K(m) for ammonia 100-fold lower than for CPSs that also use glutamine as a nitrogen donor, and required allosteric activation by N-acetylglutamate (AGA), a sensor of excess amino acids. The recent availability of a Schizosaccharomyces pombe expression system for hCPS allowed us to utilize protein engineering approaches to elucidate the distinctive hCPS properties. Although the site of AGA interaction is not defined, it is known that the binding of AGA to CPS leads to a conformational change in which a pair of cysteine side chains become proximate and can then be selectively i

SUBMITTER: Hart EJ 

PROVIDER: S-EPMC2645840 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature