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Literature summary for 2.7.1.1 extracted from

  • Grimsby, J.; Sarabu, R.; Corbett, W.L.; Haynes, N.E.; Bizzarro, F.T.; Coffey, J.W.; Guertin, K.R.; Hilliard, D.W.; Kester, R.F.; Mahaney, P.E.; Marcus, L.; Qi, L.; Spence, C.L.; Tengi, J.; Magnuson, M.A.; Chu, C.A.; Dvorozniak, M.T.; Matschinsky, F.M.; Grippo, J.F.
    Allosteric activators of glucokinase: potential role in diabetes therapy (2003), Science, 301, 370-373.
    View publication on PubMed
Search for more literature for 2.7.1.1

Activating Compound

Activating Compound Comment Organism Structure
additional information RO-28-1674 is inactive Mus musculus
additional information RO-28-1674 is inactive Homo sapiens
RO-28-0450 racemic, activates the enzyme Homo sapiens
RO-28-1675 lowers the threshold concentration of D-glucose required for insulin release from 7 mM to 3 mM in pancreatic islets in vivo, reduced blood glucose level in vivo after feeding to type 2 diabetic Goto-Kakizaki rats and supresses endogenous glucose production in ZDF-Gmi rats Rattus norvegicus
RO-28-1675 R-enantiomer, highly activates the enzyme by elevating Vmax 1.5fold and decreasing Km about 4fold, reverses enzyme inhibition by human glucokinase regulatory protein, the S-enantiomer is inactive Homo sapiens
RO-28-1675 reduced blood glucose level in vivo after feeding to type 2 diabetic mice Mus musculus

Application

Application Comment Organism
pharmacology enzyme is a target for activator drug design in therapy of type 2 diabetes mellitus Homo sapiens

Protein Variants

Protein Variants Comment Organism
A456V mutation leads to increased enzyme activity, associated with hyperinsulinism and hypoglycemia Homo sapiens
V455M mutation leads to increased enzyme activity, associated with hyperinsulinism and hypoglycemia Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
human glucokinase regulatory protein inhibition is reversed by activator RO-28-1675 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2
-
 D-glucose in presence of activator RO-28-1675 Homo sapiens
8.6
-
 D-glucose in absence of activator Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
 Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + D-glucose Mus musculus
-
 ADP + D-glucose 6-phosphate
-
 ?
ATP + D-glucose Rattus norvegicus
-
 ADP + D-glucose 6-phosphate
-
 ?
ATP + D-glucose Homo sapiens enzyme plays a key role in whole-body glucose homeostasis ADP + D-glucose 6-phosphate
-
 ?
additional information Homo sapiens loss of enzyme activity is involved in type 2 diabetes mellitus ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
 type 2 diabetic C57BL/6J mice
-
Rattus norvegicus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
hepatocyte
-
 Homo sapiens
-
pancreatic beta cell
-
 Homo sapiens
-
pancreatic beta cell
-
 Rattus norvegicus
-
pancreatic islet
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + D-glucose
-
 Mus musculus ADP + D-glucose 6-phosphate
-
 ?
ATP + D-glucose
-
 Homo sapiens ADP + D-glucose 6-phosphate
-
 ?
ATP + D-glucose
-
 Rattus norvegicus ADP + D-glucose 6-phosphate
-
 ?
ATP + D-glucose enzyme plays a key role in whole-body glucose homeostasis Homo sapiens ADP + D-glucose 6-phosphate
-
 ?
additional information loss of enzyme activity is involved in type 2 diabetes mellitus Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
GK
-
 Mus musculus
GK
-
 Homo sapiens
GK
-
 Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mus musculus
ATP
-
 Homo sapiens
ATP
-
 Rattus norvegicus