PF00310

Glutamine amidotransferases class-II

Pfam entry
Member databasePfam
Pfam typedomain
Short nameGATase_2
ClanNTN
Author Finn RD;0000-0001-8626-2148 Bateman A;0000-0002-6982-4660 Eberhardt R;0000-0001-6152-1369
Sequence Ontology0000417

Description
Imported from IPR017932

A large group of biosynthetic enzymes are able to catalyse the removal of the ammonia group from glutamine and then to transfer this group to a substrate to form a new carbon-nitrogen group. This catalytic activity is known as glutamine amidotransferase (GATase)
[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. On the basis of sequence similarities 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-II (or type 2) GATase domains have been found in the following enzymes:


 * Amido phosphoribosyltransferase (glutamine phosphoribosylpyrophosphate amidotransferase). An enzyme which catalyses the first step in purine biosynthesis, the transfer of the ammonia group of glutamine to PRPP to form 5-phosphoribosylamine (gene purF in bacteria, ADE4 in yeast).
 * Glucosamine--fructose-6-phosphate aminotransferase. This enzyme catalyses a key reaction in amino sugar synthesis, the formation of glucosamine 6-phosphate from fructose 6-phosphate and glutamine (gene glmS in Escherichia coli, nodM in Rhizobium, GFA1 in yeast).
 * Asparagine synthetase (glutamine-hydrolyzing). This enzyme is responsible for the synthesis of asparagine from aspartate and glutamine.
 * Glutamate synthase (gltS), an enzyme which participates in the ammonia assimilation process by catalysing the formation of glutamate from glutamine and 2-oxoglutarate. Glutamate synthase is a multicomponent iron-sulphur flavoprotein and three types occur which use a different electron donor: NADPH-dependent gltS (large chain), ferredoxin-dependent gltS and NADH-dependent gltS
[4]
.


The active site is formed by a cysteine present at the N-terminal extremity of the mature form of all these enzymes
[5, 6, 7, 8]
. Two other conserved residues, Asn and Gly, form an oxyanion hole for stabilisation of the formed tetrahedral intermediate. An insert of ~120 residues can occur between the conserved regions
[4]
. In some class-II GATases (for example in Bacillus subtilis or chicken amido phosphoribosyltransferase) the enzyme is synthesised with a short propeptide which is cleaved off post-translationally by a proposed autocatalytic mechanism. Nuclear-encoded Fd-dependent gltS have a longer propeptide which may contain a chloroplast-targeting peptide in addition to the propeptide that is excised on enzyme activation.

The 3-D structure of the GATase type 2 domain forms a four layer α/β/β/α architecture which consists of a fold similar to the N-terminal nucleophile (Ntn) hydrolases. These have the capacity for nucleophilic attack and the possibility of autocatalytic processing. The N-terminal position and the folding of the catalytic Cys differ strongly from the Cys-His-Glu triad which forms the active site of GATases of type 1.

References
Imported from IPR017932

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.Glutamate synthase: a complex iron-sulfur flavoprotein. Vanoni MA, Curti B. Cell. Mol. Life Sci. 55, 617-38, (1999). View articlePMID: 10357231

5.The glutamine-utilizing site of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase. Vollmer SJ, Switzer RL, Hermodson MA, Bower SG, Zalkin H. J. Biol. Chem. 258, 10582-5, (1983). View articlePMID: 6411716

6.The N-terminal cysteine of human asparagine synthetase is essential for glutamine-dependent activity. Van Heeke G, Schuster SM. J. Biol. Chem. 264, 19475-7, (1989). View articlePMID: 2573597

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

8.Glutamate synthase: a fascinating pathway from L-glutamine to L-glutamate. van den Heuvel RH, Curti B, Vanoni MA, Mattevi A. Cell. Mol. Life Sci. 61, 669-81, (2004). View articlePMID: 15052410

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