PROSITE documentation PDOC51986

Glutamine synthetase (GS) beta-grasp and catalytic domains profiles

The glutamine synthetases (GSs; EC 6.3.1.2, also known as γ-glutamyl: ammonia ligases) are a family of large oligomeric enzymes catalyzing the condensation of ammonium and glutamate, along with ATP, to form glutamine, the principal source of nitrogen for protein and nucleic acid synthesis. Because of their critical role in nitrogen metabolism, these enzymes are found in all forms of life from primitive to higher organisms, and they may be among the most ancient functioning enzymes in existence. In mammals, the activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine; there are a number of links between changes in GS activity and neurodegenerative disorders, such as Alzheimer's disease. In plants, because of its importance in the assimilation and re-assimilation of ammonia, the enzyme is a target of some herbicides. GS is also a central component of bacterial nitrogen metabolism and a potential drug target [1,2,3,4,5,6,7,8].

The GS family can be divided into three main enzyme types, easily distinguished by length: GSI with 360 amino acids on average, GSII with 450, and GSIII with 730. All of them form multimeric proteins containing double-ringed quaternary structures composed of identical units: GSI- and GSIII-type enzymes contain 12 identical subunits, whereas GSII- enzymes contain 10 identical subunits consisting of 2 pentameric rings. All three GS classes contain a homology region that consists of a regulatory N-terminal β-grasp domain and a catalytic C-terminal domain, with the N-terminal domain of one subunit and the C-terminal domain of the neighboring subunit forming an active site. The β-grasp domain consists of a five-strand antiparallel β-sheet (see <PDB:3FKY>) whereas the catalytic domain contains an eight-stranded β-sheet (see <PDB:7CPR>) [1,2,3,4,5,6,7,8].

The profiles we developed cover the entire GS β-grasp and catalytic domains.