PROSITE documentation PDOC00406

Glutamine amidotransferase type 2 domain profile




Description

A large group of biosynthetic enzymes are able to catalyze 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) (EC 2.4.2.-) [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) (see <PDOC00405>) 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) (EC 2.4.2.14). An enzyme which catalyzes 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 (EC 2.6.1.16). This enzyme catalyzes 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) (EC 6.3.5.4). 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 catalyzing the formation of glutamate from glutamine and 2-oxoglutarate. Glutamate synthase is a multicomponent iron-sulfur flavoprotein and three types occur which use a different electron donor: NADPH-dependent gltS (large chain) (EC 1.4.1.13), ferredoxin-dependent gltS (EC 1.4.7.1) and NADH-dependent gltS (EC 1.4.1.14) [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 stabilization 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 synthesized 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 additon to the propeptide that is excised on enzyme activation [4].

The 3-D structure of the GATase type 2 domain forms a four layer α/β/β/α architecture (see <PDB:1LM1>) 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 (see <PDOC00405>).

The profile we developed covers the entire GATase type 2 domain.

Last update:

November 2006 / Pattern removed, profile added and text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

GATASE_TYPE_2, PS51278; Glutamine amidotransferase type 2 domain profile  (MATRIX)


References

1AuthorsBuchanan J.M.
TitleThe amidotransferases.
SourceAdv. Enzymol. Relat. Areas Mol. Biol. 39:91-183(1973).
PubMed ID4355768

2AuthorsWeng M.L., Zalkin H.
TitleStructural role for a conserved region in the CTP synthetase glutamine amide transfer domain.
SourceJ. Bacteriol. 169:3023-3028(1987).
PubMed ID3298209

3AuthorsNyunoya H., Lusty C.J.
TitleSequence of the small subunit of yeast carbamyl phosphate synthetase and identification of its catalytic domain.
SourceJ. Biol. Chem. 259:9790-9798(1984).
PubMed ID6086650

4AuthorsVanoni M.A., Curti B.
TitleGlutamate synthase: a complex iron-sulfur flavoprotein.
SourceCell. Mol. Life Sci. 55:617-638(1999).
PubMed ID10357231

5AuthorsVollmer S.J., Switzer R.L., Hermodson M.A., Bower S.G., Zalkin H.
TitleThe glutamine-utilizing site of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase.
SourceJ. Biol. Chem. 258:10582-10585(1983).
PubMed ID6411716

6AuthorsVan Heeke G., Schuster S.M.
TitleThe N-terminal cysteine of human asparagine synthetase is essential for glutamine-dependent activity.
SourceJ. Biol. Chem. 264:19475-19477(1989).
PubMed ID2573597

7AuthorsMassiere F., Badet-Denisot M.A.
TitleThe mechanism of glutamine-dependent amidotransferases.
SourceCell. Mol. Life Sci. 54:205-222(1998).
PubMed ID9575335

8Authorsvan den Heuvel R.H.H., Curti B., Vanoni M.A., Mattevi A.
TitleGlutamate synthase: a fascinating pathway from L-glutamine to L-glutamate.
SourceCell. Mol. Life Sci. 61:669-681(2004).
PubMed ID15052410
DOI10.1007/s00018-003-3316-0



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