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Literature summary for 1.4.1.3 extracted from

  • Kanavouras, K.; Borompokas, N.; Latsoudis, H.; Stagourakis, A.; Zaganas, I.; Plaitakis, A.
    Mutations in human GLUD2 glutamate dehydrogenase affecting basal activity and regulation (2009), J. Neurochem., 109 Suppl 1, 167-173.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
ADP
-
Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
H454Y mutation in the pivot helix, mutant shows diminished basal activity and a strongly decreased maximal activity, almost no activation by L-leucine, mutant H454Y requires higher concentrations of ADP for its activation than the wild-type, mutant shows an increased resistance to GTP inhibition, mutation makes the enzyme extremely heat-labile compared to wild-type. IC50 (GTP): 2.92 Homo sapiens
K450E mutation in the pivot helix, mutant shows diminished basal activity and a strongly decreased maximal activity, no activation by L-leucine, ADP restores the decreased activity of K450E but this occurs at substantially higher concentrations compared to wild-type, mutant shows an increased resistance to GTP inhibition, mutation makes the enzyme extremely heat-labile compared to wild-type. IC50 (GTP): 180 Homo sapiens
Q441R mutation in the small helix of the antenna, basal activity increased by 2fold compared to wild-type, potentiated activation by L-leucine, Q411R substitution has little effect on the allosteric regulation of the mutant by ADP and GTP compared to wild-type, mutation makes the enzyme more resistant to thermal inactivation compared to wild-type. IC50 (GTP): 0.227 Homo sapiens
S445L mutation in the small helix of the antenna, basal activity increased by 2fold compared to wild-type, potentiated activation by L-leucine, S445L mutant retains the regulatory properties of the wild-type concerning its activation by ADP and inhibition by GTP, mutation makes the enzyme more resistant to thermal inactivation compared to wild-type. IC50 (GTP): 0.317 Homo sapiens
S448P mutation located in the junction of the antenna with the pivot helix, mutant shows reduced basal activity without significantly altering the allosteric regulation by GTP or ADP, mutant is slightly induced by L-leucine. IC50 (GTP): 0.186 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
GTP
-
Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
GLUD2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
additional information
-
Q441R or S445L mutation makes the enzyme more resistant to thermal inactivation compared to wild-type, K450E or H454Y mutation makes the enzyme extremely heat-labile compared to wild-type Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.186
-
mutant S448P, pH 8.0, 25°C Homo sapiens GTP
0.227
-
mutant Q441R, pH 8.0, 25°C Homo sapiens GTP
0.2627
-
wild-type, pH 8.0, 25°C Homo sapiens GTP
0.317
-
mutant S445L, pH 8.0, 25°C Homo sapiens GTP
2.921
-
mutant H454Y, pH 8.0, 25°C Homo sapiens GTP
180
-
mutant K450E, pH 8.0, 25°C Homo sapiens GTP