PROSITE documentation PDOC00406Glutamine amidotransferase type 2 domain profile
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.
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PROSITE method (with tools and information) covered by this documentation:
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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