IUBMB Enzyme Nomenclature

EC 6.3.5.5

Accepted name: carbamoyl-phosphate synthase (glutamine-hydrolysing)

Reaction: 2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate
(1) L-glutamine + H2O = L-glutamate + NH3
(2) 2 ATP + HCO3- = 2 ADP + phosphate + carbamoyl phosphate

For diagram of reaction click here.

Other name(s): carbamoyl-phosphate synthetase (glutamine-hydrolysing); carbamyl phosphate synthetase (glutamine); carbamoylphosphate synthetase II; glutamine-dependent carbamyl phosphate synthetase; carbamoyl phosphate synthetase; CPS; carbon-dioxide:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)

Systematic name: hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)

Comments: The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 Å in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxy phosphate to produce the carbamate intermediate. The carboxy-phosphate intermediate is formed by the phosphorylation of bicarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6].

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 37233-48-0

References:

1. Anderson, P.M. and Meister, A. Evidence for an activated form of carbon dioxide in the reaction catalysed by Escherichia coli carbamyl phosphate synthetase. Biochemistry 4 (1965) 2803-2809.

2. Kalman, S.M., Duffield, P.H. and Brzozowski, T. Purification and properties of a bacterial carbamyl phosphate synthetase. J. Biol. Chem. 241 (1966) 1871-1877. [PMID: 5329589]

3. Yip, M.C.M. and Knox, W.E. Glutamine-dependent carbamyl phosphate synthetase. Properties and distribution in normal and neoplastic rat tissues. J. Biol. Chem. 245 (1970) 2199-2204. [PMID: 5442268]

4. Stapleton, M.A., Javid-Majd, F., Harmon, M.F., Hanks, B.A., Grahmann, J.L., Mullins, L.S. and Raushel, F.M. Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. Biochemistry 35 (1996) 14352-14361. [PMID: 8916922]

5. Holden, H.M., Thoden, J.B. and Raushel, F.M. Carbamoyl phosphate synthetase: a tunnel runs through it. Curr. Opin. Struct. Biol. 8 (1998) 679-685. [PMID: 9914247]

6. Raushel, F.M., Thoden, J.B., Reinhart, G.D. and Holden, H.M. Carbamoyl phosphate synthetase: a crooked path from substrates to products. Curr. Opin. Chem. Biol. 2 (1998) 624-632. [PMID: 9818189]

7. Raushel, F.M., Thoden, J.B. and Holden, H.M. The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Biochemistry 38 (1999) 7891-7899. [PMID: 10387030]

8. Thoden, J.B., Huang, X., Raushel, F.M. and Holden, H.M. Carbamoyl-phosphate synthetase. Creation of an escape route for ammonia. J. Biol. Chem. 277 (2002) 39722-39727. [PMID: 12130656]

[EC 6.3.5.5 created 1972 as EC 2.7.2.9, transferred 1978 to EC 6.3.5.5, modified 2006]


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