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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.

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

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

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

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS51278 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51278 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51278 • Scan Swiss-Prot/TrEMBL entries against PS51278 • view ligand binding statistics

Matching PDB structures: 1AO0 1CT9 1EA0 1ECB ... [ALL]

1	Authors	Buchanan J.M.
	Title	The amidotransferases.
	Source	Adv. Enzymol. Relat. Areas Mol. Biol. 39:91-183(1973).
	PubMed ID	4355768

2	Authors	Weng M.L., Zalkin H.
	Title	Structural role for a conserved region in the CTP synthetase glutamine amide transfer domain.
	Source	J. Bacteriol. 169:3023-3028(1987).
	PubMed ID	3298209

3	Authors	Nyunoya H., Lusty C.J.
	Title	Sequence of the small subunit of yeast carbamyl phosphate synthetase and identification of its catalytic domain.
	Source	J. Biol. Chem. 259:9790-9798(1984).
	PubMed ID	6086650

4	Authors	Vanoni M.A., Curti B.
	Title	Glutamate synthase: a complex iron-sulfur flavoprotein.
	Source	Cell. Mol. Life Sci. 55:617-638(1999).
	PubMed ID	10357231

5	Authors	Vollmer S.J., Switzer R.L., Hermodson M.A., Bower S.G., Zalkin H.
	Title	The glutamine-utilizing site of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase.
	Source	J. Biol. Chem. 258:10582-10585(1983).
	PubMed ID	6411716

6	Authors	Van Heeke G., Schuster S.M.
	Title	The N-terminal cysteine of human asparagine synthetase is essential for glutamine-dependent activity.
	Source	J. Biol. Chem. 264:19475-19477(1989).
	PubMed ID	2573597

7	Authors	Massiere F., Badet-Denisot M.A.
	Title	The mechanism of glutamine-dependent amidotransferases.
	Source	Cell. Mol. Life Sci. 54:205-222(1998).
	PubMed ID	9575335

8	Authors	van den Heuvel R.H.H., Curti B., Vanoni M.A., Mattevi A.
	Title	Glutamate synthase: a fascinating pathway from L-glutamine to L-glutamate.
	Source	Cell. Mol. Life Sci. 61:669-681(2004).
	PubMed ID	15052410
	DOI	10.1007/s00018-003-3316-0

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