Carbamoyl phosphate synthetase

Function

Carbamoyl phosphate synthetase (CPS) catalyzes the production of carbamoyl phosphate from ATP, Mg+2, bicarbonate and glutamine. CPS is part of the pyrimidine and arginine biosynthesis as well as the urea cycle in vertebrates. Ornithine is an allosteric effector of CPS.[1] There are 3 forms of CPS:

  • CPS I participates in the urea cycle. CPS I uses glutamine for NH3 source.
  • CPS II participates in pyrimidine metabolism
  • CPS III is found in fish.

Disease

CPS I deficiency causes the accumulation of NH3 in the blood.

Structural highlights

CPS I and II are composed of 2 subunits. The large subunit contain active sites which bind nucleotides and other effectors. The small subunit catalyzes the hydrolysis of glutamine to glutamate and NH3. The .[2] CPS I contains a methylglyoxal synthetase (MGS) domain which binds . Water molecules are shown as red spheres.

.

.

.

3D structures of carbamoyl phosphate synthetase

Carbamoyl phosphate synthetase 3D structures


E. coli carbamoyl phosphate synthetase large chain (cyan) and small chain (salmon) complex with ADP, phosphate and ornithine, 1a9x

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Kalman SM, Duffield PH, Brzozowski T. Purification and properties of a bacterial carbamyl phosphate synthetase. J Biol Chem. 1966 Apr 25;241(8):1871-7. PMID:5329589
  2. Thoden JB, Miran SG, Phillips JC, Howard AJ, Raushel FM, Holden HM. Carbamoyl phosphate synthetase: caught in the act of glutamine hydrolysis. Biochemistry. 1998 Jun 23;37(25):8825-31. PMID:9636022 doi:http://dx.doi.org/10.1021/bi9807761

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky