F
IPR012220

Glutamate synthase, eukaryotic

InterPro entry
Short nameGlu_synth_euk

Description

This group represents the eukaryotic type of glutamate synthase (NADH-GOGAT,
1.4.1.14
). This pyridine-linked form is found in both photosynthetic and nonphotosynthetic eukaryotes. It displays a single-subunit structure corresponding to the fusion of the small and the large bacterial subunits.

Glutamate synthase (GOGAT, 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
[1]
. 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
[2]
. The small subunit functions as a FAD-dependent NADPH oxidoreductase, which serves to transfer reducing equivalents to the site of glutamate synthesis on the large subunit through the enzyme [3Fe-4S] cluster (on the large subunit) and at least one of its [4Fe-4S] centres
[3, 4]
. The large subunit contains the GltS L-glutamine amidotransferase (GAT) site where L-Gln binds and is hydrolysed to yield L-Glu and ammonia. The latter is transferred through the intramolecular ammonia tunnel
[1]
to the glutamate synthase site where 2-OG binds, is converted to the iminoglutarate (2-IG) intermediate, and reduced to L-Glu by receiving reducing equivalents from the reduced FMN cofactor at this site
[5]
.

There are four classes of GOGAT
[3, 6]
:

1. Bacterial NADPH-dependent GOGAT (NADPH-GOGAT,
1.4.1.13
). 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,
1.4.7.1
) 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,
1.4.1.14
) 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
[6, 3]
(
IPR012375
,
IPR012061
), and to the small subunit.

The large subunit of GOGAT consists of three domains: N-terminal domain (amidotransferase domain
IPR017932
); central (consisting of
IPR006982
and the FMN-binding domain
IPR002932
), and the C-terminal domain (
IPR002489
).

The N-terminal amidotransferase domain is characterised by a four layer α/β/β/α architecture and is similar to other Ntn-amidotransferases
[2]
. It contains the typical catalytic centre of Ntn-amidotransferases, and the N-terminal Cys-1 catalyses the hydrolysis of L-glutamine generating ammonia and the first molecule of L-glutamate
[2]
.

References

1.Cross-talk and ammonia channeling between active centers in the unexpected domain arrangement of glutamate synthase. Binda C, Bossi RT, Wakatsuki S, Arzt S, Coda A, Curti B, Vanoni MA, Mattevi A. Structure 8, 1299-308, (2000). View articlePMID: 11188694

2.Structural studies on the synchronization of catalytic centers in glutamate synthase. van den Heuvel RH, Ferrari D, Bossi RT, Ravasio S, Curti B, Vanoni MA, Florencio FJ, Mattevi A. J. Biol. Chem. 277, 24579-83, (2002). View articlePMID: 11967268

3.Glutamate synthase: a complex iron-sulfur flavoprotein. Vanoni MA, Curti B. Cell. Mol. Life Sci. 55, 617-38, (1999). View articlePMID: 10357231

4.Evolutionary analyses of the small subunit of glutamate synthase: gene order conservation, gene fusions, and prokaryote-to-eukaryote lateral gene transfers. Andersson JO, Roger AJ. Eukaryotic Cell 1, 304-10, (2002). View articlePMID: 12455964

5.Properties of the recombinant ferredoxin-dependent glutamate synthase of Synechocystis PCC6803. Comparison with the Azospirillum brasilense NADPH-dependent enzyme and its isolated alpha subunit. Ravasio S, Dossena L, Martin-Figueroa E, Florencio FJ, Mattevi A, Morandi P, Curti B, Vanoni MA. Biochemistry 41, 8120-33, (2002). View articlePMID: 12069605

6.Phylogenetic analyses of two "archaeal" genes in thermotoga maritima reveal multiple transfers between archaea and bacteria. Nesbo CL, L'Haridon S, Stetter KO, Doolittle WF. Mol. Biol. Evol. 18, 362-75, (2001). View articlePMID: 11230537

Further reading

7. Saccharomyces cerevisiae has a single glutamate synthase gene coding for a plant-like high-molecular-weight polypeptide. Cogoni C, Valenzuela L, Gonzalez-Halphen D, Olivera H, Macino G, Ballario P, Gonzalez A. J. Bacteriol. 177, 792-8, (1995). View articlePMID: 7836314

GO terms

Cross References

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