| 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 | |||||||||
| 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 | ||||||||
| |||||||||
| Glutamine synthetase, beta-Grasp domain | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||
| Symbol | Gln-synt_N | ||||||||||
| Pfam | PF03951 | ||||||||||
| InterPro | IPR008147 | ||||||||||
| PROSITE | PDOC00162 | ||||||||||
| SCOP2 | 2gls / SCOPe / SUPFAM | ||||||||||
| |||||||||||
| Glutamine synthetase, catalytic domain | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 12-subunit enzyme glutamine synthetase from Salmonella typhimurium.[2] | |||||||||||
| Identifiers | |||||||||||
| Symbol | Gln-synt_C | ||||||||||
| Pfam | PF00120 | ||||||||||
| Pfam clan | CL0286 | ||||||||||
| InterPro | IPR008146 | ||||||||||
| PROSITE | PDOC00162 | ||||||||||
| SCOP2 | 2gls / SCOPe / SUPFAM | ||||||||||
| |||||||||||
| glutamate-ammonia ligase (glutamine synthetase) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | GLUL | ||||||
| Alt. symbols | GLNS | ||||||
| NCBI gene | 2752 | ||||||
| HGNC | 4341 | ||||||
| OMIM | 138290 | ||||||
| PDB | 2qc8 | ||||||
| RefSeq | NM_002065 | ||||||
| UniProt | P15104 | ||||||
| Other data | |||||||
| EC number | 6.3.1.2 | ||||||
| Locus | Chr. 1 q31 | ||||||
| |||||||
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.