Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.1.1 extracted from

  • Gloyn, A.L.; Odili, S.; Zelent, D.; Buettger, C.; Castleden, H.A.; Steele, A.M.; Stride, A.; Shiota, C.; Magnuson, M.A.; Lorini, R.; dAnnunzio, G.; Stanley, C.A.; Kwagh, J.; van Schaftingen, E.; Veiga-da-Cunha, M.; Barbetti, F.; Dunten, P.; Han, Y.; Grimsby, J.; Taub, R.; Ellard, S.; Hattersley, A.T.
    Insights into the structure and regulation of glucokinase from a novel mutation (V62M), which causes maturity-onset diabetes of the young (2005), J. Biol. Chem., 280, 14105-14113.
    View publication on PubMed
Search for more literature for 2.7.1.1

Activating Compound

Activating Compound Comment Organism Structure
RO0274375 wild-type enzyme V62A, V62T, and V62L respond to the activator. V62Q, V62E, V62F, and V62K are resistant to the activators Homo sapiens
RO0281675 wild-type enzyme V62A, V62T, and V62L respond to the activator. V62Q, V62E, V62F, and V62K are resistant to the activators Homo sapiens
RO0283946 wild-type enzyme V62A, V62T, and V62L respond to the activator. V62Q, V62E, V62F, and V62K are resistant to the activators Homo sapiens

Protein Variants

Protein Variants Comment Organism
V62A kcat for ATP is 70% of wild-type value Homo sapiens
V62E kcat for ATP is 8% of wild-type value Homo sapiens
V62F no inhibition by glucokinase regulatory protein. kcat for ATP is 54% of wild-type value Homo sapiens
V62K no inhibition by glucokinase regulatory protein. kcat for ATP is 10% of wild-type value Homo sapiens
V62L no inhibition by glucokinase regulatory protein. kcat for ATP is 96% of wild-type value Homo sapiens
V62M mutation may cause hyperglycemia by a complex defect of GCK regulation involving instability in combination with loss of control by a putative endogenous activator and/or glucokinase regulatory protein. wild type enzyme is slightly activated after 30-min incubation as the temperature is raised from 30°C to 47.5°C. The activity of V62M GST-glucokinase increases similarly as that of the wild type enzyme but decreases abruptly at temperatures above 42.5°C. V62M GCK does not respond to RO0281675, nor does it respond to the hepatic glucokinase regulatory protein. kcat for ATP is 86% of wild-type value Homo sapiens
V62Q no inhibition by glucokinase regulatory protein. kcat for ATP is 24% of wild-type value Homo sapiens
V62T kcat for ATP is 41% of wild-type value Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
glucokinase regulatory protein wild type enzyme and mutant enzymes V62A, V62T, and V62E are significantly inhibited (80% enzyme activity remaining), no inhibition of V62L, V62M, V62Q, V62F, V62K Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.07
-
 ATP mutant enzyme V62E Homo sapiens
0.11
-
 ATP mutant enzyme V62Q Homo sapiens
0.16
-
 ATP mutant enzyme V62K Homo sapiens
0.2
-
 ATP mutant enzyme V62A Homo sapiens
0.22
-
 ATP mutant enzyme V62T Homo sapiens
0.41
-
 ATP wild-type enzyme Homo sapiens
0.46
-
 ATP mutant enzyme V62M Homo sapiens
0.61
-
 ATP mutant enzyme V62L Homo sapiens
0.71
-
 ATP mutant enzyme V62F Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
 GCK mutation (V62M) identified in two families
-

Purification (Commentary)

Purification (Comment) Organism
wild type, mutant V62M, and E300K GST-glucokinase proteins Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + D-glucose
-
 Homo sapiens ADP + D-glucose 6-phosphate
-
 ?

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
42.5
-
 wild-type enzyme is more stable than mutant enzyme V62M Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
additional information
-
 additional information as the temperature is raised from 30°C to 47.5°C kcat decreases, falling to about 10 per sec (by 80%) at 50°C Homo sapiens
4.92
-
 ATP mutant enzyme V62E Homo sapiens
6.42
-
 ATP mutant enzyme V62K Homo sapiens
14.9
-
 ATP mutant enzyme V62Q Homo sapiens
25.7
-
 ATP mutant enzyme V62T Homo sapiens
33.7
-
 ATP mutant enzyme V62F Homo sapiens
43.1
-
 ATP mutant enzyme V62A Homo sapiens
53.6
-
 ATP mutant enzyme V62M Homo sapiens
59.9
-
 ATP mutant enzyme V62L Homo sapiens
62.3
-
 ATP wild-type enzyme Homo sapiens