Glutamate synthase large subunit-like protein, archaeal type (GltB_archl_type)
Type: Family

This entry represents the predicted archaeal type glutamate synthase large subunit, which includes stand-alone proteins corresponding to the N-terminal, FMN-binding, and the C-terminal domains of the large subunit. All members in this entry contain the FMN-binding domain and some have 1-3 copies of 4Fe-4S binding domain in the N-terminal region but they lack the linker domain, found in the bacterial glutamate synthase large subunit .

The large (alpha, GltB) subunit of bacterial glutamate synthase (GOGAT) consists of three domains.

represents a stand-alone version of the central domain, and this subgoup contains proteins that are predicted to function as part of GOGAT. This stand-alone form occurs in the archaeal type of GOGAT, where the large subunit is represented by three separate proteins, corresponding to the three domains of the "standard" bacterial enzyme . Similar organization of GOGAT with stand-alone domains has been found in some bacteria (e.g., Sinorhizobium meliloti, Thermotoga maritima), but its function is not clear in those organisms where the "standard" bacterial form is also present (e.g., Sinorhizobium meliloti).

The second (central) domain of the bacterial GOGAT large subunit consists of a

linker domain and the FMN-binding domain (

). The FMN-binding domain has a β/α barrel topology. In this domain, the 2-iminoglutarate intermediate, formed upon the addition of ammonia onto 2-oxoglutarate, is reduced by the FMN cofactor producing the second molecule of L-glutamate . This domain also contains the enzyme 3Fe-4S cluster .

Originally, only the ORF encoding the central domain of GOGAT was recognised and annotated as GltB in archaea, and the rest of the large subunit was thought to be missing, which may lead to some misannotations . This led to speculations that the archaeal form of the GOGAT large subunit is the ancestral minimum form of the enzyme. Later analysis showed, however, that in all archaea where the large subunit has been found, its entire sequence is represented by three separate ORFs .

Glutamate synthase (GOGAT, GltS) is a complex iron-sulphur flavoprotein that catalyses the reductive synthesis of L-glutamate from 2-oxoglutarate (2-OG) and L-glutamine via intramolecular channelling of ammonia, a reaction in the bacterial, yeast and plant pathways for ammonia assimilation . GOGAT 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 .

There are four classes of GOGAT :

1. Bacterial NADPH-dependent GOGAT (NADPH-GOGAT,

). This standard bacterial NADPH-GOGAT is composed of a large (alpha, GltB) subunit and a small (beta, GltD) subunit.

2. Ferredoxin-dependent form in cyanobacteria and plants (Fd-GOGAT from photosynthetic cells,

) displays a single-subunit structure corresponding to the large bacterial subunit.

3. Pyridine-linked form in both photosynthetic and nonphotosynthetic eukaryotes (eukaryotic GOGAT or NADH-GOGAT,

) displays a single-subunit structure corresponding to the fusion of the small and the large bacterial subunits (

).

4. The archaeal type with stand-alone proteins corresponding to the N-terminal, FMN-binding, and the C-terminal domains of the large subunit (

,

,

), and to the small subunit.