Reaction: ATP + UTP + L-glutamine = ADP + phosphate + CTP + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) ATP + UTP + NH3 = ADP + phosphate + CTP
Other name(s): UTPammonia ligase; cytidine triphosphate synthetase; uridine triphosphate aminase; cytidine 5'-triphosphate synthetase; CTPS (gene name); pyrG (gene name)
Systematic name: UTP:L-glutamine amido-ligase (ADP-forming)
Comments: The enzyme contains three functionally distinct sites: an allosteric GTP-binding site, a glutaminase site where glutamine hydrolysis occurs (cf. EC 188.8.131.52, glutaminase), and the active site where CTP synthesis takes place. The reaction proceeds via phosphorylation of UTP by ATP to give an activated intermediate 4-phosphoryl UTP and ADP [4,5]. Ammonia then reacts with this intermediate generating CTP and a phosphate. The enzyme can also use ammonia from the surrounding solution [3,6].
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9023-56-7
1. Lieberman, I. Enzymatic amination of uridine triphosphate to cytidine triphosphate. J. Biol. Chem. 222 (1956) 765-775. [PMID: 13367044]
2. Long, C.W., Levitzki, A., Houston, L.L and Koshland, D.E., Jr. Subunit structures and interactions of CTP synthetase. Fed. Proc. 28 (1969) 342.
3. Levitzki, A. and Koshland, D.E., Jr. Ligand-induced dimer-to-tetramer transformation in cytosine triphosphate synthetase. Biochemistry 11 (1972) 247-253. [PMID: 4550560]
4. von der Saal, W., Anderson, P.M. and Villafranca, J.J. Mechanistic investigations of Escherichia coli cytidine-5'-triphosphate synthetase. Detection of an intermediate by positional isotope exchange experiments. J. Biol. Chem. 260 (1985) 14993-14997. [PMID: 2933396]
5. Lewis, D.A. and Villafranca, J.J. Investigation of the mechanism of CTP synthetase using rapid quench and isotope partitioning methods. Biochemistry 28 (1989) 8454-8459. [PMID: 2532543]
6. Wadskov-Hansen, S.L., Willemoes, M., Martinussen, J., Hammer, K., Neuhard, J. and Larsen, S. Cloning and verification of the Lactococcus lactis pyrG gene and characterization of the gene product, CTP synthase. J. Biol. Chem. 276 (2001) 38002-38009. [PMID: 11500486]