Human carbamoyl phosphate synthetase I (CPSI): Insights on the structural role of the unknown function domains

Carbamoyl phosphate synthetase (CPS) is an ancient protein. In mammals it intervenes in the urea cycle. This enzyme is organized into six domains, three of which have no established role in the mammalian enzyme. Taking advantage of the high degree of conservation between the human and the Escherichia coli homologue a comparative study was carried out in order to infer about the biological role of these less characterized domains. We show that among the residues involved in the maintenance of quaternary structure of the E. coli enzyme, several are highly conserved between human and bacterial enzyme and match the homologous positions of the “unknown function” domains in human enzyme, suggesting they are involved in the structural stability of the human enzyme as they are in bacteria.

► Carbamoyl phosphate synthetase I (CPSI) is a highly conserved ancient protein.
► Residues with structural roles in Escherichia coli CPS are conserved in the human CPSI.
► We propose these residues are critical structural elements in human enzyme.