Glutamine synthetase

Glutamine synthetase,
beta-Grasp domain
Glutamine synthetase,; beta-Grasp domain
Identifiers
Symbol	Gln-synt_N
Pfam	PF03951
InterPro	IPR008147
PROSITE	PDOC00162
SCOP2	2gls / SCOPe / SUPFAM
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1f1h, 1f52, 1fpy, 1hto, 1lgr, 2bvc, 2gls, 2qc8, 2ojw

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PubMed	articles
NCBI	proteins

glutamate—ammonia ligase
glutamate—ammonia ligase
	Active site between two monomers of glutamine synthetase from Salmonella typhimurium. Cation binding sites are yellow and orange; ADP is pink; phosphinothricin is blue.
Identifiers
EC no.	6.3.1.2
CAS no.	9023-70-5
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
PMC
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PubMed	articles
NCBI	proteins

Glutamine synthetase,
catalytic domain

12-subunit enzyme glutamine synthetase from Salmonella typhimurium.^[2]

Identifiers

Symbol

Gln-synt_C

Pfam clan

2gls / SCOPe / SUPFAM

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1f1h, 1f52, 1fpy, 1hto, 1lgr, 2bvc, 2gls, 2qc8, 2ojw

glutamate-ammonia ligase (glutamine synthetase)

Identifiers

Symbol

GLUL

Alt. symbols

GLNS

Other data

Chr. 1 q31

Search for
Structures	Swiss-model
Domains	InterPro

Glutamine synthetase (GS) (EC 6.3.1.2)^[3] is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine:

Glutamate + ATP + NH₃ → Glutamine + ADP + phosphate

Glutamine synthetase uses ammonia produced by nitrate reduction, amino acid degradation, and photorespiration.^[4] The amide group of glutamate is a nitrogen source for the synthesis of glutamine pathway metabolites.^[5]

Other reactions may take place via GS. Competition between ammonium ion and water, their binding affinities, and the concentration of ammonium ion, influences glutamine synthesis and glutamine hydrolysis. Glutamine is formed if an ammonium ion attacks the acyl-phosphate intermediate, while glutamate is remade if water attacks the intermediate.^[6]^[7] Ammonium ion binds more strongly than water to GS due to electrostatic forces between a cation and a negatively charged pocket.^[4] Another possible reaction is upon NH₂OH binding to GS, rather than NH₄+, yields γ-glutamylhydroxamate.^[6]^[7]

^ PDB: 1FPY; Gill HS, Eisenberg D (February 2001). "The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition". Biochemistry. 40 (7): 1903–12. doi:10.1021/bi002438h. PMID 11329256.
^ PDB: 2GLS; Yamashita MM, Almassy RJ, Janson CA, Cascio D, Eisenberg D (October 1989). "Refined atomic model of glutamine synthetase at 3.5 A resolution". J. Biol. Chem. 264 (30): 17681–90. doi:10.2210/pdb2gls/pdb. PMID 2572586.
^ Eisenberg D, Almassy RJ, Janson CA, Chapman MS, Suh SW, Cascio D, Smith WW (1987). "Some evolutionary relationships of the primary biological catalysts glutamine synthetase and RuBisCO". Cold Spring Harb. Symp. Quant. Biol. 52: 483–90. doi:10.1101/sqb.1987.052.01.055. PMID 2900091.
^ ^a ^b Liaw SH, Kuo I, Eisenberg D (Nov 1995). "Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site". Protein Sci. 4 (11): 2358–65. doi:10.1002/pro.5560041114. PMC 2143006. PMID 8563633.
^ Liaw SH, Pan C, Eisenberg D (Jun 1993). "Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine". Proc. Natl. Acad. Sci. USA. 90 (11): 4996–5000. Bibcode:1993PNAS...90.4996L. doi:10.1073/pnas.90.11.4996. PMC 46640. PMID 8099447.
^ ^a ^b Eisenberg D, Gill HS, Pfluegl GM, Rotstein SH (Mar 2000). "Structure-function relationships of glutamine synthetases". Biochim Biophys Acta. 1477 (1–2): 122–45. doi:10.1016/S0167-4838(99)00270-8. PMID 10708854.
^ ^a ^b Liaw SH, Eisenberg D (Jan 1994). "Structural model for the reaction mechanism of glutamine synthetase, based on five crystal structures of enzyme-substrate complexes". Biochemistry. 33 (3): 675–81. doi:10.1021/bi00169a007. PMID 7904828.

[pmid11329256-1] PDB: 1FPY; Gill HS, Eisenberg D (February 2001). "The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition". Biochemistry. 40 (7): 1903–12. doi:10.1021/bi002438h. PMID 11329256.

[pmid2572586-2] PDB: 2GLS; Yamashita MM, Almassy RJ, Janson CA, Cascio D, Eisenberg D (October 1989). "Refined atomic model of glutamine synthetase at 3.5 A resolution". J. Biol. Chem. 264 (30): 17681–90. doi:10.2210/pdb2gls/pdb. PMID 2572586.

[pmid2900091-3] Eisenberg D, Almassy RJ, Janson CA, Chapman MS, Suh SW, Cascio D, Smith WW (1987). "Some evolutionary relationships of the primary biological catalysts glutamine synthetase and RuBisCO". Cold Spring Harb. Symp. Quant. Biol. 52: 483–90. doi:10.1101/sqb.1987.052.01.055. PMID 2900091.

[pmid8563633-4] Liaw SH, Kuo I, Eisenberg D (Nov 1995). "Discovery of the ammonium substrate site on glutamine synthetase, a third cation binding site". Protein Sci. 4 (11): 2358–65. doi:10.1002/pro.5560041114. PMC 2143006. PMID 8563633.

[pmid8099447-5] Liaw SH, Pan C, Eisenberg D (Jun 1993). "Feedback inhibition of fully unadenylylated glutamine synthetase from Salmonella typhimurium by glycine, alanine, and serine". Proc. Natl. Acad. Sci. USA. 90 (11): 4996–5000. Bibcode:1993PNAS...90.4996L. doi:10.1073/pnas.90.11.4996. PMC 46640. PMID 8099447.

[pmid10708854-6] Eisenberg D, Gill HS, Pfluegl GM, Rotstein SH (Mar 2000). "Structure-function relationships of glutamine synthetases". Biochim Biophys Acta. 1477 (1–2): 122–45. doi:10.1016/S0167-4838(99)00270-8. PMID 10708854.

[pmid7904828-7] Liaw SH, Eisenberg D (Jan 1994). "Structural model for the reaction mechanism of glutamine synthetase, based on five crystal structures of enzyme-substrate complexes". Biochemistry. 33 (3): 675–81. doi:10.1021/bi00169a007. PMID 7904828.

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