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Literature summary for 1.4.1.3 extracted from

  • Plaitakis, A.; Spanaki, C.; Mastorodemos, V.; Zaganas, I.
    Study of structure-function relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissue-specific (GLUD2) isoenzyme (2003), Neurochem. Int., 43, 401-410.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
ADP in absence of GTP the isoenzyme GLUD2 assumes a conformational state associated with little catalytic activity, it remains amenable to full activation by ADP and/or L-Leu Homo sapiens
L-Leu 0.3-10 mM stimulates isoenzyme GLUD2 to a greater extent than isoenzyme GLUD1 Homo sapiens
L-Leu 0.3-10 mM stimulates isoenzyme GLUD2 to a greater extent than isoenzyme GLUD1. In absence of GTP the isoenzyme GLUD2 assumes a conformational state associated with little catalytic activity, it remains amenable to full activation by ADP and/or L-Leu Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression in Sf9 cells using the baculovirus expression system Homo sapiens

Protein Variants

Protein Variants Comment Organism
G456A mutant enzyme is resistant to GTP Homo sapiens
R443S mutation abolishes basal activity and renders the enzyme dependent on ADP for function Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
GTP potent inhibitor. IC50 for wild-type enzyme is 0.00019 mM, IC50 for mutant enzyme G456A is 0.0028 mM. ADP renders the GLUD1-derived enzyme less sensitive to GTP inhibition; totally insensitive to, it becomes amenable to GTP inhibition in presence of ADP Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P00367
-
-
Homo sapiens P49448
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
astrocyte predominantly Homo sapiens
-
brain
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2-oxoglutarate + NADH + NH3
-
Homo sapiens L-glutamate + NAD+ + H2O
-
?

Synonyms

Synonyms Comment Organism
GLUD1 wildely expressed isoenzyme Homo sapiens
GLUD2 nerve-tissue-specific isoenzyme Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
7 8 25-30% less active at pH 7.0 than at pH 7.5 and 8.0 Homo sapiens
7 8 equally active at pH 7.0 and 8.0 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADH
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00019
-
potent inhibitor. IC50 for wild-type enzyme is 0.00019 mM Homo sapiens GTP
0.0028
-
IC50 for mutant enzyme G456A is 0.0028 mM. ADP renders the GLUD1-derived enzyme less sensitive to GTP inhibition Homo sapiens GTP