Pathways & interactions
Glutamate synthase, alpha subunit, C-terminal domain superfamily (IPR036485)
Short name: Glu_synth_asu_C_sf
- Glutamate synthase, alpha subunit, C-terminal (IPR002489)
- Formylmethanofuran dehydrogenase, fused subunit C/D (IPR012048)
- Glutamate synthase, large subunit domain 3 stand-alone protein (IPR012061)
- Glutamate synthase, large subunit domains 1/3 fusion (IPR012075)
- Glutamate synthase, eukaryotic (IPR012220)
- Formylmethanofuran dehydrogenase subunit C (IPR017550)
- Archael gltB (IPR035710)
Glutamate synthase (GltS) is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate and L-glutamine via intramolecular channelling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation [PMID: 11188694]. GltS is a multifunctional enzyme that functions through three distinct active centres carrying out multiple reaction steps: L-glutamine hydrolysis, conversion of 2-oxoglutarate into L-glutamate, and electron uptake from an electron donor. The active centres are synchronised to avoid the wasteful consumption of L-glutamine [PMID: 11967268]. There are three classes of GltS, which share many functional properties: bacterial NADPH-dependent GltS, ferredoxin-dependent GltS from photosynthetic cells, and NAD(P)H-dependent GltS from yeast, fungi and lower animals.
The dimeric alpha subunits each consist of four domains: N-terminal amidotransferase domain, the central domain, the FMN binding domain and the C-terminal domain. The C-terminal domain forms a right-handed beta-helix that comprises seven helical turns [PMID: 11188694]. Each helical turn has a sharp bend that is associated with a repeated sequence motif consisting of G-XX-G-XXX-G. This domain does not contain any residues directly involved in catalysis, but has a crucial structural role.
This domain superfamily is also found in proteins such as subunit C of formylmethanofuran dehydrogenase, which catalyses the first step in methane formation from carbon dioxide in methanogenic archaea. There are two isoenzymes of formylmethanofuran dehydrogenase: a tungsten-containing isoenzyme (FwdC) and a molybdenum-containing isoenzyme (FmdC). The tungsten isoenzyme is constitutively transcribed, whereas transcription of the molybdenum operon is induced by molybdate [PMID: 9818358].