Glutamine synthetase

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.[1]
Identifiers
EC no.6.3.1.2
CAS no.9023-70-5
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
Glutamine synthetase,
beta-Grasp domain
Identifiers
SymbolGln-synt_N
PfamPF03951
InterProIPR008147
PROSITEPDOC00162
SCOP22gls / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1f1h​, 1f52​, 1fpy​, 1hto​, 1lgr​, 2bvc​, 2gls​, 2qc8​, 2ojw
Glutamine synthetase,
catalytic domain
12-subunit enzyme glutamine synthetase from Salmonella typhimurium.[2]
Identifiers
SymbolGln-synt_C
PfamPF00120
Pfam clanCL0286
InterProIPR008146
PROSITEPDOC00162
SCOP22gls / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1f1h​, 1f52​, 1fpy​, 1hto​, 1lgr​, 2bvc​, 2gls​, 2qc8​, 2ojw
glutamate-ammonia ligase (glutamine synthetase)
Identifiers
SymbolGLUL
Alt. symbolsGLNS
NCBI gene2752
HGNC4341
OMIM138290
PDB2qc8
RefSeqNM_002065
UniProtP15104
Other data
EC number6.3.1.2
LocusChr. 1 q31
Search for
StructuresSwiss-model
DomainsInterPro

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 reaction.
Glutamine synthetase catalyzed reaction

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]

  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.
  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.
  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.
  4. ^ 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.
  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.
  6. ^ 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.
  7. ^ 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.