D
IPR017926

Glutamine amidotransferase

InterPro entry
Short nameGATASE
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
[1]
. 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
[2, 3]
: class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). Class-I (or type 1) GATase domains have been found in the following enzymes:


 * The second component of anthranilate synthase (AS)
[4]
. AS catalyses the biosynthesis of anthranilate from chorismate and glutamine. AS is generally a dimeric enzyme: the first component can synthesize anthranilate using ammonia rather than glutamine, whereas component II provides the GATase activity
[5]
. In some bacteria and in fungi the GATase component of AS is part of a multifunctional protein that also catalyses other steps of the biosynthesis of tryptophan.
 * The second component of 4-amino-4-deoxychorismate (ADC) synthase, a dimeric prokaryotic enzyme that functions in the pathway that catalyses the biosynthesis of para-aminobenzoate (PABA) from chorismate and glutamine. The second component (gene pabA) provides the GATase activity
[4]
.
 * CTP synthase. CTP synthase catalyses the final reaction in the biosynthesis of pyrimidine, the ATP-dependent formation of CTP from UTP and glutamine. CTP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the C-terminal section
[2]
.
 * GMP synthase (glutamine-hydrolyzing). GMP synthase catalyses the ATP-dependent formation of GMP from xanthosine 5'-phosphate and glutamine. GMP synthase is a single chain enzyme that contains two distinct domains; the GATase domain is in the N-terminal section
[6, 7]
.
 * Glutamine-dependent carbamoyl-phosphate synthase (GD-CPSase); an enzyme involved in both arginine and pyrimidine biosynthesis and which catalyses the ATP-dependent formation of carbamoyl phosphate from glutamine and carbon dioxide. In bacteria GD-CPSase is composed of two subunits: the large chain (gene carB) provides the CPSase activity, while the small chain (gene carA) provides the GATase activity. In yeast the enzyme involved in arginine biosynthesis is also composed of two subunits: CPA1 (GATase), and CPA2 (CPSase). In most eukaryotes, the first three steps of pyrimidine biosynthesis are catalysed by a large multifunctional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals). The GATase domain is located at the N-terminal extremity of this polyprotein
[8]
.
 * Phosphoribosylformylglycinamidine synthase, an enzyme that catalyses the fourth step in the de novo biosynthesis of purines. In some species of bacteria and archaea, FGAM synthase II is composed of two subunits: a small chain (gene purQ) which provides the GATase activity and a large chain (gene purL) which provides the aminator activity. In eukaryotes and Gram-negative bacteria a single polypeptide (large type of purL) contains a FGAM synthetase domain and the GATase as the C-terminal domain
[9]
.
 * Imidazole glycerol phosphate synthase subunit hisH, an enzyme that catalyses the fifth step in the biosynthesis of histidine.


A triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity
[7, 10]
. Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.

References

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

2.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

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.Evolution of a biosynthetic pathway: the tryptophan paradigm. Crawford IP. Annu. Rev. Microbiol. 43, 567-600, (1989). View articlePMID: 2679363

5.The crystal structure of anthranilate synthase from Sulfolobus solfataricus: functional implications. Knochel T, Ivens A, Hester G, Gonzalez A, Bauerle R, Wilmanns M, Kirschner K, Jansonius JN. Proc. Natl. Acad. Sci. U.S.A. 96, 9479-84, (1999). View articlePMID: 10449718

6.Identification of a trpG-related glutamine amide transfer domain in Escherichia coli GMP synthetase. Zalkin H, Argos P, Narayana SV, Tiedeman AA, Smith JM. J. Biol. Chem. 260, 3350-4, (1985). View articlePMID: 2982857

7.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

8.The evolutionary history of the first three enzymes in pyrimidine biosynthesis. Davidson JN, Chen KC, Jamison RS, Musmanno LA, Kern CB. Bioessays 15, 157-64, (1993). View articlePMID: 8098212

9.Domain organization of Salmonella typhimurium formylglycinamide ribonucleotide amidotransferase revealed by X-ray crystallography. Anand R, Hoskins AA, Stubbe J, Ealick SE. Biochemistry 43, 10328-42, (2004). View articlePMID: 15301531

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

Cross References

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