Application | Comment | Organism |
---|---|---|
drug development | the enzyme is a target for design of structure-based specific inhibitors | Homo sapiens |
drug development | the enzyme is a target for design of structure-based specific inhibitors | Canis lupus familiaris |
Crystallization (Comment) | Organism |
---|---|
apo-enzyme structure determination and analysis at resolution of 3.0 A, molecular replacement using a pentamer of Zea mays GS/MnADP/MSO-P complex, overview | Canis lupus familiaris |
two different enzyme complexes with: 1. phosphate, ADP, and manganese, and 2. a phosphorylated form of the inhibitor methionine sulfoximine, ADP and manganese. X-ray diffraction structure determination and analysis at resolutions of 2.05 A and 2.6 A, respectively, molecular replacement | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | design and construction of structure-based inhibitors targeting the nucleotide binding site, which varies to a large degree between mammalian and bacterial enzymes | Canis lupus familiaris | |
additional information | design and construction of structure-based inhibitors targeting the nucleotide binding site, which varies to a large degree between mammalian and bacterial enzymes | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Homo sapiens | |
Mg2+ | the active site of the apoenzyme structure contains only a single Mg2+, rather than Mn2+, ion bound at the n1 position | Canis lupus familiaris | |
Mn2+ | three enzyme-bound Mn2+ ions, an additional Mn2+ ion makes contacts with Glu196 and the inorganic phosphate | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-glutamate + NH3 | Homo sapiens | the enzyme activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine, enzyme activity defects are linked to neurodegenerative disorders, such as Alzheimer's disease, overview | ADP + phosphate + L-glutamine | - |
? | |
ATP + L-glutamate + NH3 | Canis lupus familiaris | the enzyme activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine, enzyme activity defects are linked to neurodegenerative disorders, such as Alzheimer's disease, overview | ADP + phosphate + L-glutamine | - |
? | |
additional information | Canis lupus familiaris | the role of GS in humans depends on tissue localization. In the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia | ? | - |
? | |
additional information | Homo sapiens | the role of GS in humans depends on tissue localization. In the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, one of the enzymes is responsible for the removal of ammonia | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Canis lupus familiaris | Q8HZM5 | - |
- |
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Homo sapiens | - |
brain | - |
Canis lupus familiaris | - |
liver | - |
Homo sapiens | - |
liver | - |
Canis lupus familiaris | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-glutamate + NH3 | the enzyme activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine, enzyme activity defects are linked to neurodegenerative disorders, such as Alzheimer's disease, overview | Homo sapiens | ADP + phosphate + L-glutamine | - |
? | |
ATP + L-glutamate + NH3 | the enzyme activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine, enzyme activity defects are linked to neurodegenerative disorders, such as Alzheimer's disease, overview | Canis lupus familiaris | ADP + phosphate + L-glutamine | - |
? | |
ATP + L-glutamate + NH3 | loop movements near the active site generate more closed forms of the eukaryotic enzyme when substrates are bound | Homo sapiens | ADP + phosphate + L-glutamine | - |
? | |
ATP + L-glutamate + NH3 | loop movements near the active site generate more closed forms of the eukaryotic enzyme when substrates are bound | Canis lupus familiaris | ADP + phosphate + L-glutamine | - |
? | |
additional information | the role of GS in humans depends on tissue localization. In the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia | Canis lupus familiaris | ? | - |
? | |
additional information | the role of GS in humans depends on tissue localization. In the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, one of the enzymes is responsible for the removal of ammonia | Homo sapiens | ? | - |
? | |
additional information | active site structure analysis, conformational changes near the active sites upon ligand binding, overview | Homo sapiens | ? | - |
? | |
additional information | active site structure analysis, conformational changes near the active sites upon ligand binding, overview | Canis lupus familiaris | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | structure analysis, and comparison of mammalian, plant, and bacterial structures, overview | Homo sapiens |
More | structure analysis, and comparison of mammalian, plant, and bacterial structures, overview | Canis lupus familiaris |
pentadecamer | structure modelling of a structure consisting of three pentamers, overview | Canis lupus familiaris |
Synonyms | Comment | Organism |
---|---|---|
gamma-glutamyl:ammonia ligase | - |
Homo sapiens |
gamma-glutamyl:ammonia ligase | - |
Canis lupus familiaris |
Glutamine synthetase | - |
Homo sapiens |
Glutamine synthetase | - |
Canis lupus familiaris |
Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
---|---|---|---|
56 | 71.5 | the melting temperature Tm for the enzyme in absence of ligands is 56°C, glutamine or glutamate have no appreciable effect on the Tm. Addition of Mg2+ at concentrations of 500 mM causes an increase of about 2°C. The Tm increases by 4.1°C and 11.5°C upon the addition of 1 mM MnCl2 and 1 mM ATP, respectively. Addition of MnCl2 and ATP together increases the Tm of HsGS by 15.5°C | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens | |
ATP | - |
Canis lupus familiaris |