D
IPR035686

Carbamoyl-phosphate synthase small subunit, GATase1 domain

InterPro entry
Short nameCPSase_GATase1
Overlapping
homologous
superfamilies
 
domain relationships

Description

Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group
[5]
. The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified
[1, 3]
: class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). In class I glutamine amidotransferases, a triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity
[4, 7]
. Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.

The E.coli carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine or ammonia, and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates
[2, 6]
. The small subunit catalyses the hydrolysis of glutamine to ammonia, which in turn used by the large chain to synthesize carbamoyl phosphate. The C-terminal domain of the small subunit of CPSase has glutamine amidotransferase activity.

References

1.Structural role for a conserved region in the CTP synthetase glutamine amide transfer domain. Weng ML, Zalkin H. J. Bacteriol. 169, 3023-8, (1987). View articlePMID: 3298209

2.The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. Raushel FM, Thoden JB, Holden HM. Biochemistry 38, 7891-9, (1999). View articlePMID: 10387030

3.Sequence of the small subunit of yeast carbamyl phosphate synthetase and identification of its catalytic domain. Nyunoya H, Lusty CJ. J. Biol. Chem. 259, 9790-8, (1984). View articlePMID: 6086650

4.The crystal structure of GMP synthetase reveals a novel catalytic triad and is a structural paradigm for two enzyme families. Tesmer JJ, Klem TJ, Deras ML, Davisson VJ, Smith JL. Nat. Struct. Biol. 3, 74-86, (1996). View articlePMID: 8548458

5.The amidotransferases. Buchanan JM. Adv. Enzymol. Relat. Areas Mol. Biol. 39, 91-183, (1973). PMID: 4355768

6.Carbamoyl phosphate synthetase: an amazing biochemical odyssey from substrate to product. Holden HM, Thoden JB, Raushel FM. Cell. Mol. Life Sci. 56, 507-22, (1999). View articlePMID: 11212301

7.The mechanism of glutamine-dependent amidotransferases. Massiere F, Badet-Denisot MA. Cell. Mol. Life Sci. 54, 205-22, (1998). View articlePMID: 9575335

Further reading

8. Structure, functional characterization, and evolution of the dihydroorotase domain of human CAD. Grande-Garcia A, Lallous N, Diaz-Tejada C, Ramon-Maiques S. Structure 22, 185-98, (2014). View articlePMID: 24332717

Cross References

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