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) and class-II (also known as purF-type or Ntn) (see <PDOC00406>). Class-I (or type 1) GATase domains have been found in the following enzymes:

• The second component of anthranilate synthase (AS) (EC 4.1.3.27) [4]. AS catalyzes 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 (see <PDB:1QDL; B>) [5]. In some bacteria and in fungi the GATase component of AS is part of a multifunctional protein that also catalyzes other steps of the biosynthesis of tryptophan.
• The second component of 4-amino-4-deoxychorismate (ADC) synthase (EC 4.1.3. -), a dimeric prokaryotic enzyme that functions in the pathway that catalyzes the biosynthesis of para-aminobenzoate (PABA) from chorismate and glutamine. The second component (gene pabA) provides the GATase activity [4].
• CTP synthase (EC 6.3.4.2). CTP synthase catalyzes 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] (see <PDB:1S1M>).
• GMP synthase (glutamine-hydrolyzing) (EC 6.3.5.2). GMP synthase catalyzes 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] (see <PDB:1GPM>).
• Glutamine-dependent carbamoyl-phosphate synthase (EC 6.3.5.5) (GD-CPSase); an enzyme involved in both arginine and pyrimidine biosynthesis and which catalyzes 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 (see <PDB:1A9X; B>). 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 catalyzed 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 (EC 6.3.5.3), an enzyme that catalyzes 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 synthethase domain and the GATase as the C-terminal domain (see <PDB:1T3T>) [9].
• Imidazole glycerol phosphate synthase subunit hisH (EC 2.4.2.-), an enzyme that catalyzes the fifth step in the biosynthesis of histidine (see <PDB:1JVN>).

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.

The profile we developed covers the entire GATase type 1 domain, including the catalytic Cys in the N-terminal half of the domain and the conserved His and Glu of the triad in the C-terminal part of the domain.