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Literature summary for 6.3.1.2 extracted from

  • Krajewski, W.W.; Collins, R.; Holmberg-Schiavone, L.; Jones, T.A.; Karlberg, T.; Mowbray, S.L.
    Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design (2008), J. Mol. Biol., 375, 217-228.
    View publication on PubMed

Application

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 (Commentary)

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

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

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Canis lupus familiaris Q8HZM5
-
-
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-
brain
-
Canis lupus familiaris
-
liver
-
Homo sapiens
-
liver
-
Canis lupus familiaris
-

Substrates and Products (Substrate)

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

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

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 [°C]

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

Cofactor Comment Organism Structure
ATP
-
Homo sapiens
ATP
-
Canis lupus familiaris