Information on EC 2.7.1.2 - glucokinase

New: Word Map on EC 2.7.1.2
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.7.1.2
-
RECOMMENDED NAME
GeneOntology No.
glucokinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
ordered mechanism in which glucose binds first and glucose 6-phosphate dissociates last
-
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
catalytic mechanism, substrate D-glucose interacts with Asn99, Asp100, Glu157, His160, and Glu187
P0A6V9
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
positive cooperation, mechanism
-
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
rapid equilibrium-ordered bi bi sequential mechanism, formation of a ternary complex of enzyme-D-glucose-MgATP2-
P0A4E1
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
rapid equilibrium-ordered bi bi sequential mechanism, formation of a ternary complex of enzyme-D-glucose-MgATP2-
-
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
the enzyme activity requires 3 cysteine residues C175, C177, and C182 within the motif CXCGX(2)GCXE that discriminates microbial glucokinases into two lineages
P54495
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
cutting-edge high-resolution nuclear magnetic resonance methods are used to explore the kinetic properties of glucokinase. Glucokinase samples a range of conformational states in the absence of glucose. In the presence of glucose or a small-molecule activator, the enzyme population shifts towards a more narrow, well-structured ensemble of states
-
ATP + D-glucose = ADP + D-glucose 6-phosphate
show the reaction diagram
using intrinsic tryptophan fluorescence a conformational change induced by the binding of adenine nucleotides to human pancreatic glucokinase is determined. The molecular dynamic simulations indicate that the binding triggers molecular motion of the flexible surface /active site loop and partial closure of the interdomain active site cleft. The modelled structure of the hGK-ATP binary complex shows the residue contacts involved in ATP binding at the active site
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
1,3-propanediol biosynthesis (engineered)
-
-
Amino sugar and nucleotide sugar metabolism
-
-
Bifidobacterium shunt
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
Butirosin and neomycin biosynthesis
-
-
Galactose metabolism
-
-
GDP-glucose biosynthesis
-
-
glucose and glucose-1-phosphate degradation
-
-
glycogen degradation I
-
-
glycogen metabolism
-
-
Glycolysis / Gluconeogenesis
-
-
glycolysis III (from glucose)
-
-
glycolysis VI (metazoan)
-
-
heterolactic fermentation
-
-
Metabolic pathways
-
-
Microbial metabolism in diverse environments
-
-
Starch and sucrose metabolism
-
-
Streptomycin biosynthesis
-
-
sucrose biosynthesis II
-
-
sucrose degradation III (sucrose invertase)
-
-
trehalose degradation I (low osmolarity)
-
-
trehalose degradation II (trehalase)
-
-
trehalose degradation IV
-
-
trehalose degradation V
-
-
UDP-N-acetyl-D-galactosamine biosynthesis II
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:D-glucose 6-phosphotransferase
A group of enzymes found in invertebrates and microorganisms that are highly specific for glucose.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GlcK
P54495
-
Glk1
A1Z0M6
-
GlkB
Q53Y25
-
glucokinase
-
-
glucokinase
P35557
-
glucokinase (phosphorylating)
-
-
-
-
glucokinase 1
-
-
glucokinase 1
P35557
-
glucokinase B
Q53Y25
-
hexokinase IV
-
-
hexokinase IV
Q53Y25
-
hexokinase IV
-
-
kinase, gluco- (phosphorylating)
-
-
-
-
TcGlcK
Q4E4E1
-
CAS REGISTRY NUMBER
COMMENTARY
9001-36-9
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain O157:H7
Uniprot
Manually annotated by BRENDA team
several strains
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
children with congenital hyperinsulinism
-
-
Manually annotated by BRENDA team
type 2 diabetic C57BL/6J mice
-
-
Manually annotated by BRENDA team
Paracoccus versutus A2
A2
-
-
Manually annotated by BRENDA team
strain KT2440
-
-
Manually annotated by BRENDA team
strain KT2440 and isogenic mutant strains, gene glk
-
-
Manually annotated by BRENDA team
OMZ70, ATCC 33535
-
-
Manually annotated by BRENDA team
no isozymes
SwissProt
Manually annotated by BRENDA team
strain PCC 6803, gene sll0593
-
-
Manually annotated by BRENDA team
gene TM 1469
-
-
Manually annotated by BRENDA team
gene TM 1469 or glk
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
6-N-(carboxyethyl)ATP + D-glucose
6-N-(carboxyethyl)ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
6-N-(carboxymethyl)ATP + D-glucose
6-N-(carboxymethyl)ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
6-N-(succinyl)ATP + D-glucose
6-N-(succinyl)ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
6-N-[N-(6-aminohexhyl)carbamoyl]ATP + D-glucose
6-N-[N-(6-aminohexhyl)carbamoyl]ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
adenosine 5'-triphosphate-polyamidoamine dendrimer + D-glucose
adenosine 5'-diphosphate-polyamidoamine dendrimer + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
ir
ATP + 2-deoxy-D-glucose
ADP + 2-deoxy-D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
-
ATP + 2-deoxy-D-glucose
ADP + 2-deoxy-D-glucose 6-phosphate
show the reaction diagram
-
26% of the activity with D-glucose
-
-
ir
ATP + 2-deoxy-D-glucose
ADP + 2-deoxy-D-glucose 6-phosphate
show the reaction diagram
-
no reaction with the recombinant enzyme
-
-
-
ATP + 2-deoxy-D-glucose
ADP + 2-deoxy-D-glucose 6-phosphate
show the reaction diagram
-
sugar binding to recombinant wild-type and mutant glucokinase monitored by kinetic measurement and tryptophan fluorescence
-
-
?
ATP + beta-D-glucose
ADP + beta-D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-fructose
ADP + D-fructose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-fructose
ADP + D-fructose 6-phosphate
show the reaction diagram
A0SZU9
-
-
-
?
ATP + D-fructose
ADP + D-fructose 6-phosphate
show the reaction diagram
-
no reaction with the recombinant enzyme
-
-
-
ATP + D-glucosamine
ADP + D-glucosamine 6-phosphate
show the reaction diagram
-
no reaction with the recombinant enzyme
-
-
-
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P0A6V9
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P35557
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P17709
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
ir
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Q92407
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P0A4E1
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P54495
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Q4E4E1
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
A0SZU9
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Q53Y25
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
highly specific for D-glucose
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
highly specific for D-glucose
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
highly specific for D-glucose
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
highly specific for D-glucose
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
ATP is the most efficient phosphoryl donor
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
phosphorylates alpha-D-glucose and beta-D-glucose equally fast
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
enzyme plays a key role in whole-body glucose homeostasis
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the enzyme catalyzes the first step of the Embden-Meyerhoff pathway and the Entner-Douderoff pathway
-
-
ir
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the pancreatic enzyme is imporatnt as glucose sensor in insulin secretion and blood glucose homeostasis, interaction of ATP and glucose during binding to the enzyme
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P0A6V9
specific for D-glucose, substrate binding site structure
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the enzyme is specific for D-glucose
-
-
ir
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the enzyme initiates the intracellular glucose catabolism/metabolism, overview
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Q4Q1I9
enzyme is only able to phosphorylate glucose
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
enzyme is only able to phosphorylate glucose
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
sugar binding to recombinant wild-type and mutant glucokinase monitored by kinetic measurement and tryptophan fluorescence
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Paracoccus versutus A2
-
ATP is the most efficient phosphoryl donor
-
-
?
ATP + D-mannose
ADP + D-mannose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-mannose
ADP + D-mannose 6-phosphate
show the reaction diagram
A0SZU9
-
-
-
?
ATP + D-mannose
ADP + D-mannose 6-phosphate
show the reaction diagram
-
no reaction with the recombinant enzyme
-
-
-
ATP + D-mannose
ADP + D-mannose 6-phosphate
show the reaction diagram
-
sugar binding to recombinant wild-type and mutant glucokinase monitored by kinetic measurement and tryptophan fluorescence
-
-
?
ATP + mannoheptulose
?
show the reaction diagram
-
sugar binding to recombinant wild-type and mutant glucokinase monitored by kinetic measurement and tryptophan fluorescence
-
-
?
ATP + N-acetyl-alpha-D-glucosamine
ADP + N-acetyl-alpha-D-glucosamine 6-phosphate
show the reaction diagram
-
at pH 7.6: 50% of the activity with alpha-D-glucose, at pH 9.0: 5% of the activity with alpha-D-glucose
-
-
?
ATP + N-acetyl-alpha-D-glucosamine
ADP + N-acetyl-alpha-D-glucosamine 6-phosphate
show the reaction diagram
-
sugar binding to recombinant wild-type and mutant glucokinase monitored by kinetic measurement and tryptophan fluorescence
-
-
?
CTP + D-glucose
CDP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
CTP + D-glucose
CDP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
CTP + D-glucose
CDP + D-glucose 6-phosphate
show the reaction diagram
-
less than 10% of the activity with ATP
-
-
?
CTP + D-glucose
CDP + D-glucose 6-phosphate
show the reaction diagram
-
10% of the activity with ATP
-
-
?
CTP + D-glucose
CDP + D-glucose 6-phosphate
show the reaction diagram
-
5% of the activity with ATP as phosphoryl donor
-
-
?
CTP + D-glucose
CDP + D-glucose 6-phosphate
show the reaction diagram
Paracoccus versutus A2
-
-
-
-
?
D-glucose + ATP
ADP + D-glucose 6-phosphate
show the reaction diagram
A1Z0M6
-
-
-
?
GTP + D-glucose
GDP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
GTP + D-glucose
GDP + D-glucose 6-phosphate
show the reaction diagram
-
30% of the activity with ATP
-
-
?
GTP + D-glucose
GDP + D-glucose 6-phosphate
show the reaction diagram
-
no reaction with the recombinant enzyme
-
-
-
GTP + D-glucose
GDP + D-glucose 6-phosphate
show the reaction diagram
-
less than 10% of ATP
-
-
?
GTP + D-glucose
GDP + D-glucose 6-phosphate
show the reaction diagram
-
12% of the activity with ATP as phosphoryl donor
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
-
30% of the activity with ATP
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
-
75% of the activity with ATP
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
-
less than 10% of the activity with ATP
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
-
20% of the activity with ATP as phosphoryl donor
-
-
?
UTP + D-glucose
UDP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
UTP + D-glucose
UDP + D-glucose 6-phosphate
show the reaction diagram
-
12% of the activity with ATP
-
-
?
UTP + D-glucose
UDP + D-glucose 6-phosphate
show the reaction diagram
-
32% of the activity with ATP
-
-
?
UTP + D-glucose
UDP + D-glucose 6-phosphate
show the reaction diagram
-
no reaction with the recombinant enzyme
-
-
-
UTP + D-glucose
UDP + D-glucose 6-phosphate
show the reaction diagram
-
less than 10% of the activity with ATP
-
-
?
UTP + D-glucose
UDP + D-glucose 6-phosphate
show the reaction diagram
-
12% of the activity with ATP as phosphoryl donor
-
-
?
ITP + D-glucose
IDP + D-glucose 6-phosphate
show the reaction diagram
Paracoccus versutus A2
-
30% of the activity with ATP
-
-
?
additional information
?
-
-
less than 10% of the activity with ATP: TTP
-
-
-
additional information
?
-
-
less than 10% of the activity with ATP: TTP
-
-
-
additional information
?
-
-
enzyme reacts equally well with ATP, UTP, GTP, ITP and CTP
-
-
-
additional information
?
-
-
not: mannose, fructose, 2-deoxyglucose, UTP, ITP, GTP
-
-
-
additional information
?
-
-
loss of enzyme activity is involved in type 2 diabetes mellitus
-
-
-
additional information
?
-
-
comparison of the biochemical properties to those of the enzyme from Streptomyces coelicolor
-
-
-
additional information
?
-
P0A4E1
comparison of the biochemical properties to those of the enzyme from Streptomyces peucetius var. caesius
-
-
-
additional information
?
-
-
no activity with D-mannose and D-fructose as phosphoryl acceptors, no activity with UDP, ADP, acetyl phosphate, and diphosphate as phosphoryl donors
-
-
-
additional information
?
-
-
no activity with fructose, galactose, and mannose, development of a coupled assay method with glucose 6-phosphate dehydrogenase stable at pH 6.8-8.5 and 75-90C, overview
-
-
-
additional information
?
-
-
recombinant enzymes NanK and YajF also utilize N-acetyl-D-mannosamine and D-fructose as substrates, respectively
-
-
-
additional information
?
-
A1Z0M6
hexokinase, Hxk1, but not the glucokinase, Glk1, is required for normal growth and sugar metabolism, and for pathogenicity on fruits
-
-
-
additional information
?
-
-
biophysical characterization of the interaction between GK and GKRP and its modulation by physiological and pharmacological effectors
-
-
-
additional information
?
-
Paracoccus versutus A2
-
less than 10% of the activity with ATP: TTP
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P0A6V9
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P35557
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P17709
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
ir
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Q92407
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P0A4E1
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
P54495
-
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
enzyme plays a key role in whole-body glucose homeostasis
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the enzyme catalyzes the first step of the Embden-Meyerhoff pathway and the Entner-Douderoff pathway
-
-
ir
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the pancreatic enzyme is imporatnt as glucose sensor in insulin secretion and blood glucose homeostasis, interaction of ATP and glucose during binding to the enzyme
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
-
the enzyme initiates the intracellular glucose catabolism/metabolism, overview
-
-
?
ATP + D-glucose
ADP + D-glucose 6-phosphate
show the reaction diagram
Paracoccus versutus A2
-
-
-
-
?
additional information
?
-
-
loss of enzyme activity is involved in type 2 diabetes mellitus
-
-
-
additional information
?
-
A1Z0M6
hexokinase, Hxk1, but not the glucokinase, Glk1, is required for normal growth and sugar metabolism, and for pathogenicity on fruits
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
as MgATP2-, binding site structure, ATP binding involves residues Asp78, Thr82, Gly227, Thr228, and S336
ATP
P54495
dependent on
ATP
-
dependent on
ATP
P0A6V9
dependent on, binding site structure
ATP
P0A4E1
as MgATP2-
CTP
-
5% of the activity with ATP
GTP
-
12% of the activity with ATP
UTP
-
12% of the activity with ATP
ITP
-
20% of the activity with ATP
additional information
-
adenosine 5'-triphosphate-polyamidoamine dendrimer, polymer-bound ATP by direct coupling, kinetics and initial reaction rates differ from ATP
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
34% of the activation with Mg2+
Ca2+
-
no activation
Cd2+
-
can partially replace Mn2+ in activation
Co2+
-
more efficient than Mg2+ in activation, relative rate 264%
Co2+
-
38.5% of the activity with Mn2+
Co2+
-
68% of the activity with Mg2+
Co2+
-
50% of the activity with Mg2+
Fe2+
-
48% of the activation with Mg2+
KCl
-
at 20 mM
Mg2+
-
completely dependent on presence of Mg2+
Mg2+
-
less efficient in activation than Mn2+ or Co2+
Mg2+
-
little or no activity with cations other than Mg2+ or Mn2+
Mg2+
-
absolute requirement for divalent cation, 78% of the activity with Mn2+; Km: 0.27 mM
Mg2+
-
at 4.4 mM MgCl2
Mg2+
-
as MgATP2-, binding site structure
Mg2+
-
at 10 mM MgCl2
Mg2+
-
most efficient divalent cation
Mg2+
-
at 4 mM MgCl2
Mg2+
P0A4E1
as MgATP2-
Mg2+
-
-
Mn2+
-
more efficient than Mg2+ in activation, relative rate 173%
Mn2+
-
absolute requirement for divalent cation, Mn2+ most effective
Mn2+
-
45% of the activity with Mg2+
Mn2+
-
90% of the activity with Mg2+
Ni2+
-
can partially replace Mn2+ in activation
Ni2+
-
20% of the activity with Mg2+
Sr2+
-
11% of the activation with Mg2+
Zn2+
-
56% of the activation with Mg2+
Zn2+
-
no activation
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
-
6-Amino-6-deoxy-D-glucose
-
noncompetitive to ATP and competitive to glucose
adenosine 5'-diphosphate-polyamidoamine dendrimer
-
product inhibition
-
ADP
-
noncompetitive to ATP and uncompetitive to glucose
beta,gamma-methyleneadenosine 5'-thiophosphate
-
noncompetitive to ATP and uncompetitive to glucose
CTP
-
in presence of ATP
CTP
-
above 1 mM, irrespective of glucose concentration
D-fructose 6-phosphate
-
weak
D-glucose 6-phosphate
-
competitive inhibitor to glucose and noncompetitive to ATP
D-glucose 6-phosphate
-
-
D-glucose 6-phosphate
-
weak
D-glucose 6-phosphate
-
-
D-glucose 6-phosphate
-
-
D-glucose 6-phosphate
-
-
GK regulatory protein
-
-
-
GKRP
-
GK regulatory protein, relative inhibition of glucokinase activity through GKRP alone wild-type: 32.5% and GKRP plus 10 microM sorbitol 6-phosphate: 55
-
glucokinase regulatory protein
-
human, i.e. GKRP, recombinantly expressed in Escherichia coli, competitive to glucose, strong inhibition in absence of fructose 6-phosphate or sorbitol 6-phosphate, the protein also binds fructose 1-phosphate and chloride are reversing the inhibition
-
glucokinase regulatory protein
-
i.e. GKRP, recombinantly expressed in Escherichia coli, inhibition in absence of fructose 6-phosphate or sorbitol 6-phosphate, competitive to D-glucose, fructose 1-phosphate and chloride are reversing the inhibition
-
glucokinase regulatory protein
-
of human or rat origin, inhibits the wild-type enzyme in presence or absence of sorbitol 6-phosphate, no inhibition of mutant V62M by both proteins
-
GTP
-
in presence of ATP
GTP
-
above 1 mM, irrespective of glucose concentration
human glucokinase regulatory protein
-
inhibition is reversed by activator RO-28-1675
-
ITP
-
in presence of ATP
N-acetyl-alpha-D-glucosamine
-
-
N-acetylglucosamine
-
weak
N-acetylglucosamine
-
-
N-ethylmaleimide
-
-
p-chlormercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
palmitoyl-CoA
-
glucokinase is inhibited by endogenous long-chain fatty acyl-CoA in islets from omega3-depleted rats
Trehalose 6-phosphate
A1Z0M6
-
TTP
-
in presence of ATP
TTP
-
above 1 mM, irrespective of glucose concentration
UTP
-
in presence of ATP
UTP
-
above 1 mM, irrespective of glucose concentration
XTP
-
in presence of ATP
ITP
-
above 1 mM, irrespective of glucose concentration
additional information
-
not: glucose or ATP up to 15 mM, mannose, fructose, 2-deoxyglucose, GDP, IDP, CDP, UDP, adenosine monophosphate, deoxyadenosine monophosphate, 3',5'-adenosine monophosphate, inorganic phosphate
-
additional information
-
catabolite repression of the glucokinase pathway and the TOL pathway is triggered by two different catabolite repression systems, repression of the glucokinase pathway is channeled through Crc
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(S)-3-(4-((3-fluoropyrrolidin-1-yl)sulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(thiazol-2-yl)benzamide
-
activation: 1.9fold
(S)-3-(4-((3-fluoropyrrolidin-1-yl)sulfonyl)phenoxy)-N-(5-fluorothiazol-2-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 2.2fold
(S)-6-(3-cyclopentyl-2-[4-(trifluoromethyl)-1H-imidazol-1-yl]propanamido)nicotinic acid
-
in the presence of liver-specific GKA, progress curves at 1 mM glucose are similar to those at 5 mM, reflecting activation of GK. With steady-state kinetic methods it is shown that there are at least two kinetically distinct forms of glucokinase that interconvert through a slow conformational change and that this interconversion is affected by glucose concentration and a liver-specific GKA
-
(Z)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-(2-methylpropylidene)-4-oxo-4,5-dihydro thiazol-2-yl)-3-(tetrahydro-2Hpyran-4-yl)propanamide
-
activation: 1.17fold
(Z)-N-(5-benzylidene-4-oxo-4,5-dihydrothiazol-2-yl)-2-(4-(cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.24fold
2-(4-(cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2Hpyran-4-yl)-N-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)propanamide
-
activation: 2.27fold
2-(4-(cyclopropylsulfonyl)phenyl)-N-(4-(prop-1-en-2-yl)thiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 2.4fold
2-(4-(cyclopropylsulfonyl)phenyl)-N-(4-isopropylthiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 2.97fold
2-(4-(cyclopropylsulfonyl)phenyl)-N-(4-oxo-4,5-dihydrothiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.65fold
2-(4-(cyclopropylsulfonyl)phenyl)-N-(5,6-dihydro-4Hcyclopenta[d]thiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 3.4fold
2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-iodo-4-isopropylhiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.34fold
-
2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c] pyridin-2-yl)-3-(tetrahydro-2Hpyran-4-yl)propanamide
-
activation: 2.26fold
2-(4-(methylsulfonyl)phenyl)-N-(4-phenylthiazol-2-yl)-3-(tetrahydro-2H-pyran-4-yl)-propanamide
-
activation: 1.3fold
2-amino-4-fluoro-5-(1-methyl-1H-imidazol-2-ylsulfanyl)-N-thiazol-2-yl-benzamide
-
potent synthetic allosteric activator, acts on the wild-type and the N-terminal deletion mutants DELTA N1-11 and DELTA N1-15, mechanism of activation
2-[4-(methylsulfonyl)phenyl]-3-(tetrahydro-2H-pyran-4-yl)-N-(1,3-thiazol-2-yl)propanamide
-
activation: 2.45fold
3-((3-methylbut-2-en-1-yl)oxy)-5-(4-(morpholinosulfonyl)phenoxy)-N-(thiazol-2-yl)benzamide
-
activation: 2.1fold
3-(4-(((2S,6R)-2,6-dimethylmorpholino)sulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(thiazol-2-yl)benzamide
-
activation: 1.5fold
3-(4-(((2S,6R)-2,6-dimethylmorpholino)sulfonyl)phenoxy)-N-(5-fluorothiazol-2-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 1.7fold
3-(4-((4-methoxypiperidin-1-yl)sulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(thiazol-2-yl)benzamide
-
activation: 1.7fold
3-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-ylsulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(thiazol-2-yl)benzamide
-
activation: 1.7fold
3-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-ylsulfonyl)phenoxy)-N-(5-fluorothiazol-2-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 1.9fold
3-(4-(cyclopropylsulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(4-oxo-4,5-dihydrothiazol-2-yl)benzamide
-
activation: 1.5fold
3-(4-(cyclopropylsulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(5-methylpyrazin-2-yl)benzamide
-
activation: 1.6fold
3-(4-(cyclopropylsulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)-N-(thiazol-2-yl)benzamide
-
activation: 2.4fold
-
3-(4-(cyclopropylsulfonyl)phenoxy)-N-(1,5-dimethyl-1H-pyr-azol-3-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 1.5fold
3-(4-(cyclopropylsulfonyl)phenoxy)-N-(4-(4-fluorophenyl)thiazol-2-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 0.9fold
N-(4,5-dimethylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.72fold
N-(4-(4-fluorophenyl)thiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.25fold
N-(4-(4-methoxyphenyl)thiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.22fold
N-(4-(tert-butyl)thiazol-2-yl)-3-(4-(cyclopropylsulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 0.7fold
N-(4-cyclopropylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.87fold
N-(4-ethylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)-propanamide
-
activation: 2.17fold
N-(4-isobutylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)-propanamide
-
activation: 2.05fold
N-(4-isopropylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)-propanamide
-
activation: 2.49fold
N-(4-tert-butylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)-propanamide
-
activation: 1.29fold
N-(5-bromo-4-isopropylthiazol-2-yl)-2-(4-(cyclopropylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.67fold
-
N-(5-fluorothiazol-2-yl)-3-((3-methylbut-2-en-1-yl)oxy)-5-(4-(morpholinosulfonyl)phenoxy)benzamide
-
activation: 1.8fold
N-(5-fluorothiazol-2-yl)-3-(4-((4-methoxypiperidin-1-yl)sulfonyl)phenoxy)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 1.7fold
N-(5-isopropyl-4-methylthiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.13fold
N-(6-fluorobenzo[d]thiazol-2-yl)-2-(4-(methylsulfonyl)phenyl)-3-(tetrahydro-2H-pyran-4-yl)propanamide
-
activation: 1.3fold
RO-0274375
-
synthetic activator, activation of wild-type enzyme and mutants V62A, V62T, and V62L, no activation of mutants V62Q, V62E, V62F, and V62K
-
RO-028165
-
synthetic activator, activation of wild-type enzyme and mutants V62A, V62T, and V62L, no activation of mutants V62Q, V62E, V62F, and V62K
-
RO-0283946
-
synthetic activator, activation of wild-type enzyme and mutants V62A, V62T, and V62L, no activation of mutants V62Q, V62E, V62F, and V62K
-
RO-28-0450
-
racemic, activates the enzyme
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
RO-28-1675
-
reduced blood glucose level in vivo after feeding to type 2 diabetic mice
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
3-(4-(cyclopropylsulfonyl)phenoxy)-N-(5-fluorothiazol-2-yl)-5-((3-methylbut-2-en-1-yl)oxy)benzamide
-
activation: 1.8fold
additional information
-
RO-28-1674 is inactive
-
additional information
-
the enzyme is 2.12fold induced by growth on glucose compared to citrate
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.9
2-deoxy-D-glucose
-
30C, pH 7.5, S151A
18
2-deoxyglucose
-
30C, pH 7.5, wild-type
0.5
6-N-(carboxyethyl)ATP
-
-
0.67
6-N-(carboxyethyl)ATP
-
-
0.55
6-N-(carboxymethyl)ATP
-
-
0.65
6-N-(carboxymethyl)ATP
-
-
0.38
6-N-(succinyl)ATP
-
-
1
6-N-(succinyl)ATP
-
-
0.5
6-N-[N-(6-aminohexhyl)carbamoyl]ATP
-
-
1.25
6-N-[N-(6-aminohexhyl)carbamoyl]ATP
-
-
0.15
alpha-D-glucose
-
30C, pH 7.6
0.00000023
ATP
-
wild-type in the presence of 20-30% glycerol, pH and temperature not specified in the publication
0.0000003
ATP
-
mutant W99R/W257F in the presence of 20-30% glycerol, pH and temperature not specified in the publication
0.00000035
ATP
-
wild-type in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000046
ATP
-
wild-type, pH and temperature not specified in the publication
0.00000049
ATP
-
mutant W99R/W257F in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000055
ATP
-
mutant W99R/W257F in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000057
ATP
-
wild-type in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000071
ATP
-
mutant W167F/W257F in the presence of 20-30% glycerol, pH and temperature not specified in the publication; mutant W99R/W167F in the presence of 20-30% glycerol, pH and temperature not specified in the publication
0.00000078
ATP
-
mutant W99R/W257F, pH and temperature not specified in the publication
0.00000109
ATP
-
mutant W167F/W257F in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000143
ATP
-
mutant W167F/W257F in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication; mutant W99R/W167F in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000163
ATP
-
mutant W167F/W257F, pH and temperature not specified in the publication
0.00000294
ATP
-
mutant W99R/W167F in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.00000335
ATP
-
mutant W99R/W167F, pH and temperature not specified in the publication
0.04
ATP
-
wild-type, 37C, pH not specified in the puclication. Kinetic constants at high and low concentrations of the fixed substrate: 0.5 mM D-glucose
0.05
ATP
P17709
-
0.07
ATP
-
recombinant mutant V62E
0.11
ATP
-
recombinant mutant V62Q
0.16
ATP
-
recombinant mutant V62K
0.16
ATP
Q53Y25
mutant enzyme V182L, glutathione S-transferase glucokinase B fusion protein
0.16
ATP
-
wild-type, 37C, pH not specified in the puclication; wild-type, 37C, pH not specified in the puclication. Kinetic constants at high and low concentrations of the fixed substrate: 60 mM D-glucose
0.189
ATP
-
pH 8.0, 85C, recombinant enzyme
0.2
ATP
-
recombinant mutant V62A
0.21
ATP
-
22C, pH 7.5
0.21
ATP
Q53Y25
mutant enzyme Y61S, glutathione S-transferase glucokinase B fusion protein
0.22
ATP
-
recombinant mutant V62T
0.24
ATP
-
mutant L146R, 37C, pH not specified in the puclication
0.26
ATP
-
recombinant Glk, pH 7.6, 25C
0.27
ATP
-
30C, pH 7.5, N166R
0.31
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant 454-Ala; pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant G68V
0.32
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S64P
0.35
ATP
Q4Q1I9
-
0.35
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant A456V; pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant K140E
0.36
ATP
-
recombinant enyme, pH 7.3, 80C
0.36
ATP
-
-
0.38
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V455M
0.39
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant G68K
0.4
ATP
-
30C, pH 7
0.4
ATP
Q53Y25
mutant enzyme E265K, glutathione S-transferase glucokinase B fusion protein
0.4
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197E
0.41
ATP
-
recombinant wild-type enzyme
0.41
ATP
Q53Y25
mutant enzyme K420E, glutathione S-transferase glucokinase B fusion protein
0.45
ATP
Q53Y25
wild-type glutathione S-transferase glucokinase B fusion protein
0.46
ATP
-
recombinant mutant V62M
0.46
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, wild-type
0.48
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V91L
0.5
ATP
-
50C, pH 8
0.5
ATP
-
-
0.51
ATP
-
recombinant YajF, pH 7.6, 25C
0.52
ATP
A0SZU9
pH 9.0, 30C
0.52
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V62M
0.53
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V452L
0.57
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant T65I
0.58
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y215A
0.61
ATP
-
recombinant mutant V62L
0.63
ATP
-
30C, pH 7.5, wild-type
0.63
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S263P
0.69
ATP
Q53Y25
mutant enzyme A379V, glutathione S-transferase glucokinase B fusion protein
0.71
ATP
-
recombinant mutant V62F
0.72
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant G72R
0.75
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant C252Y
0.76
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V389L
0.8
ATP
-
30C, pH 7
0.87
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant A379T
0.89
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant C213R
0.92
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y214A
1.08
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y214C
1.1
ATP
-
20C pH 7
1.31
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197L
1.39
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197I
1.42
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y214A/V452A
1.5
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant E442K
1.52
ATP
-
30C, pH 7.5, N166R-S151A
1.53
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant K414E
1.59
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S64Y
2.08
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant P417R
2.21
ATP
-
30C, pH 7.5, S151A
2.26
ATP
-
30C, pH 7.5, S151G
2.6
ATP
-
30C, pH 7.5, S151C
2.71
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197I/A379T
2.9
ATP
-
recombinant NanK, pH 7.6, 25C
3.32
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M298K
3.4
ATP
-
recombinant YcfX, pH 7.6, 25C
3.76
ATP
-
pH 7.65
12.6
ATP
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S336L
0.56
CTP
-
30C, pH 7
4.7
D-fructose
-
30C, pH 7.5, N166R-S151A
7.7
D-fructose
-
30C, pH 7.5, S151G
57.3
D-fructose
-
30C, pH 7.5, S151A
77
D-fructose
-
30C, pH 7.5, N166R
240
D-fructose
-
30C, pH 7.5, wild-type and S151C
0.028
D-glucose
P17709
-
0.038
D-glucose
-
pH 8.0, 85C, recombinant enzyme
0.048
D-glucose
A1Z0M6
-
0.054
D-glucose
-
50C, pH 8
0.063
D-glucose
Q92407
-
0.076
D-glucose
-
recombinant Glk, pH 7.6, 25C
0.095
D-glucose
-
30C, pH 7
0.11
D-glucose
-
+ CTP, 30C, pH 7
0.12
D-glucose
-
20C pH 7
0.12
D-glucose
-
+ UTP, 30C, pH 7
0.15
D-glucose
-
-
0.15
D-glucose
-
30C, pH 7.5, S151G and N1166R-S151A
0.2
D-glucose
-
+ ITP, 30C, pH 7
0.22
D-glucose
-
-
0.22
D-glucose
-
cosubstrate GTP, 30C, pH 7
0.31
D-glucose
-
recombinant YajF, pH 7.6, 25C
0.31
D-glucose
A0SZU9
pH 9.0, 30C
0.34
D-glucose
-
30C, pH 7.5, S151A
0.5
D-glucose
-
+ ATP, 30C, pH 7
0.61
D-glucose
-
22C, pH 7.5
0.61
D-glucose
-
-
0.78
D-glucose
-
pH 7.65
0.86
D-glucose
-
-
1
D-glucose
-
recombinant enyme, pH 7.3, 80C
1
D-glucose
-
-
2
D-glucose
-
in presence of activator RO-28-1675
2.1
D-glucose
-
30C, pH 7.5, S151C and N166R
2.5 - 5
D-glucose
Q4Q1I9
recombinant enzyme without His6
3.3
D-glucose
Q4Q1I9
recombinant (His)6-tagged enzyme
3.8
D-glucose
-
recombinant YcfX, pH 7.6, 25C
6
D-glucose
-
30C, pH 7.5, wild-type
7.4
D-glucose
-
31C and pH 7.7, fetal glucokinase
7.7
D-glucose
-
31C and pH 7.7, adult glucokinase
8.6
D-glucose
-
in absence of activator
18
D-glucose
-
recombinant NanK, pH 7.6, 25C
0.08
D-mannose
-
30C, pH 7.5, N166R-S151A
0.12
D-mannose
-
30C, pH 7.5, S151G
0.21
D-mannose
-
30C, pH 7.5, S151A
2.2
D-mannose
-
30C, pH 7.5, N166R
3.74
D-mannose
-
30C, pH 7.5, S151C
4.4
D-mannose
-
30C, pH 7.5, wild-type
0.25
GTP
-
30C, pH 7
0.36
ITP
-
30C, pH 7
0.63
UTP
-
30C, pH 7
0.19
MgATP2-
-
30C, pH 7
additional information
additional information
-
kinetics
-
additional information
additional information
-
wild-type and mutant enzymes, cooperative/sigmoidal glucose-dependent kinetics
-
additional information
additional information
-
kinetics with cofactor ATP and with adenosine 5'-triphosphate-polyamidoamine dendrimer as cofactor, overview
-
additional information
additional information
-
kinetic analysis, wild-type and mutant enzymes, overview
-
additional information
additional information
-
activation energy, kinetics
-
additional information
additional information
P0A4E1
kinetic mechanism
-
additional information
additional information
-
kinetic mechanism
-
additional information
additional information
-
positive cooperation, mechanism, kinetic model
-
additional information
additional information
-
kinetic constants of TcGlcK obtained for different anomer solutions of D-glucose
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.61
ATP
-
mutant L146R, 37C, pH not specified in the puclication
0.7
ATP
-
wild-type, 37C, pH not specified in the puclication. Kinetic constants at high and low concentrations of the fixed substrate: 0.5 mM D-glucose
68.4
ATP
-
wild-type, 37C, pH not specified in the puclication; wild-type, 37C, pH not specified in the puclication. Kinetic constants at high and low concentrations of the fixed substrate: 60 mM D-glucose
317
ATP
Q4Q1I9
-
1492
ATP
-
-
5.9
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W167F in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
6.1
beta-D-glucose
-
co-substrate: ATP, mutant W167F/W257F in the presence of 20-30% glycerol, pH and temperature not specified in the publication
6.37
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W167F in the presence of 20-30% glycerol, pH and temperature not specified in the publication
8.47
beta-D-glucose
-
co-substrate: ATP, mutant W167F/W257F, pH and temperature not specified in the publication
9.43
beta-D-glucose
-
co-substrate: ATP, mutant W167F/W257F in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
11.1
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W167F in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
12.4
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W167F, pH and temperature not specified in the publication
12.7
beta-D-glucose
-
co-substrate: ATP, mutant W167F/W257F in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
26.2
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W257F in the presence of 20-30% glycerol, pH and temperature not specified in the publication
37.7
beta-D-glucose
-
co-substrate: ATP, wild-type in the presence of 20-30% glycerol, pH and temperature not specified in the publication
38.9
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W257F in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
60.5
beta-D-glucose
-
co-substrate: ATP, wild-type in the presence of 20-30% glycerol and in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
69.9
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W257F, pH and temperature not specified in the publication
83.7
beta-D-glucose
-
co-substrate: ATP, wild-type, pH and temperature not specified in the publication
91.3
beta-D-glucose
-
co-substrate: ATP, mutant W99R/W257F in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
166
beta-D-glucose
-
co-substrate: ATP, wild-type in the presence of 20 microM glucokinase activator drug (GKA), pH and temperature not specified in the publication
0.007
D-glucose
-
mutant T228M, 37C, pH not specified in the puclication
0.77
D-glucose
-
mutant L146R, 37C, pH not specified in the puclication
2.46
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S336L
4.92
D-glucose
-
recombinant mutant V62E
6.42
D-glucose
-
recombinant mutant V62K
9.1
D-glucose
-
recombinant NanK, pH 7.6, 25C
9.2
D-glucose
-
recombinant YcfX, pH 7.6, 25C
12
D-glucose
-
recombinant Glk, pH 7.6, 25C
14.9
D-glucose
-
recombinant mutant V62Q
17.7
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197E
19.9
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant K414E
22.6
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant T65I
23.1
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y214A/V452A
25.7
D-glucose
-
recombinant mutant V62T
29.3
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant C252Y
29.8
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant G72R
33.7
D-glucose
-
recombinant mutant V62F
37.7
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M298K
40
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant K140E
43.1
D-glucose
-
recombinant mutant V62A
43.2
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant G68K
44.6
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S263P
44.7
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y215A
47.2
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V62M
48.3
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant P417R
50
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant C213R
50.2
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197I/A379T
52.2
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant 454-Ala
52.6
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant E442K
53.6
D-glucose
-
recombinant mutant V62M
58.1
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197I
59.9
D-glucose
-
recombinant mutant V62L
60.6
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V91L
61.2
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant A379T
61.8
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V455M
62.3
D-glucose
-
recombinant wild-type enzyme
62.6
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant M197L
62.7
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant G68V
62.8
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, wild-type
65.3
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y214C
65.6
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant A456V
67.1
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V389L
67.6
D-glucose
-
wild-type, 37C, pH not specified in the puclication
83.3
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S64P
92.6
D-glucose
-
pH 8.0, 85C, recombinant enzyme
114
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant S64Y
117
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant Y214A
122
D-glucose
-
pH 7.1, temperature not specified in the publication, co-substrate: ATP, mutant V452L
317
D-glucose
Q4Q1I9
-
410
D-glucose
-
recombinant Glk, pH 7.6, 25C
1492
D-glucose
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000128
GK regulatory protein
-
steady-state Ki value, pH 7.1, 25C
-
0.000113
GK regulatory protein
-
initial Ki value, pH 7.1, 25C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0001
-
fetal glucokinase
0.0003
-
adult glucokinase
0.0018
-
strain KT2440, grown on citrate
0.0164
-
strain KT440 in presence of glucose and toluene
0.0211
-
strain KT2440, grown on glucose
0.0273
-
strain KT440 in presence of glucose
0.26
-
hepatocytes
0.34
-
S151G, D-mannose as substrate
0.57
-
rat hepatocytes treated with adenovirus containing the entire coding sequence of rat liver glucokinase
0.6
-
S151G, D-glucose as substrate
0.786
A0SZU9
substrate: D-fructose
0.941
A0SZU9
subatrste: D-mannose
1.09
-
purified enzyme, Vmax
1.4
-
N166R-S151A, D-mannose as substrate
1.67
P0A4E1
purified enzyme, Vmax
1.95
A0SZU9
substrate: D-glucose
2
-
N166R-S151A, D-glucose as substrate
2.16
-
S151C, D-mannose as substrate
3.18
-
S151G, D-fructose as substrate
3.32
-
S151A, D-mannose as substrate
4.1
-
S151A, 2-deoxy-D-glucose as substrate
6
-
S151C, D-glucose as substrate
6.6
-
S151A, D-glucose as substrate
9.12
-
S151C, D-fructose as substrate
14.5
-
N166R-S151A, D-fructose as substrate
23.8
-
S151A, D-fructose as substrate
47.2
-
recombinant protein
60.8
-
N166R, D-mannose as substrate
68
-
wild-type, D-mannose and 2-deoxy-D-glucose as substrate
80
-
wild-type and N166R, D-glucose as substrate
122
-
wild-type, D-fructose as substrate
166
-
purified recombinant enzyme
310
-
N166R, D-fructose as substrate
370
-
purified recombinant enzyme, Vmax
additional information
-
Vmax of wild-type and mutant enzymes
additional information
-
activity of the enzyme in isogenic mutants with mutations in the glucose metabolism network, overview
additional information
-
determination of glucokinase activity in glucose metabolism, KT2440 metabolizes glucose and toluene simultaneously, the effect of toluene on glucose metabolism is directed to the glucokinase branch repressing glucokinase activity, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
2 optima: a major peak at pH 7.0 and a minor peak at pH 8.2
7
-
assay at
7.1
-
assay at
7.1
-
assay at
7.2
-
assay at
7.4
-
assay at
7.5
P54495
assay at
7.5
-
assay at
7.6
-
assay at
7.6
-
assay at
7.8
-
assay at
8
-
sharp optimum
8.2
-
2 optima: a major peak at pH 7.0 and a minor peak at pH 8.2
8.5 - 9
Q4Q1I9
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 10.5
-
pH 6.0: about 30% of activity maximum, pH 10.5: about 80% of activity maximum
6 - 9
-
pH 6.0: about 55% of activity maximum, pH 9.0: about 75% of activity maximum
6.8 - 7.7
-
50% activity at pH 6.8 and pH 7.7
additional information
-
development of an assay method stable at pH 6.8-8.5 and 75-90C, overview
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
38 - 98
-
below 10% of maximal activity at 38C, about 90% of maximal activity at 98C
additional information
-
development of an assay method stable at pH 6.8-8.5 and 75-90C, overview
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
O31392
glk is a nonessential gene that is constitutively expressed during logarithmic growth and has slightly reduced expression in the stationary phase
Manually annotated by BRENDA team
-
the rate of glucose phosphorylation in hepatocytes is determined by the subcellular location of glucokinase and by its association with its regulatory protein (GKRP) in the nucleus. Elevated glucose concentrations and precursors of fructose 1-phosphate (e.g., sorbitol) cause dissociation of glucokinase from GKRP and translocation to the cytoplasm. Mechanisms downstream of AMPK activation, involving phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and GKRP are involved in the ATP-independent inhibition of glucose-induced glucokinase translocation by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside in hepatocytes
Manually annotated by BRENDA team
-
glucokinase is inhibited by endogenous long-chain fatty acyl-CoA in islets from omega3-depleted rats. Such an inhibition probably participates to the alteration of D-glucose catabolism prevailing in these islets
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
P0A4E1
over 96% of the enzyme content in the cell
Manually annotated by BRENDA team
-
over 96% of the enzyme content in the cell
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Lactococcus lactis subsp. lactis (strain IL1403)
Lactococcus lactis subsp. lactis (strain IL1403)
Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Streptomyces griseus subsp. griseus (strain JCM 4626 / NBRC 13350)
Streptomyces griseus subsp. griseus (strain JCM 4626 / NBRC 13350)
Streptomyces griseus subsp. griseus (strain JCM 4626 / NBRC 13350)
Trypanosoma cruzi (strain CL Brener)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
gel filtration
641062
35000
P54495
recombinant enzyme, oxidative conditions, PAGE, the wild-type and mutant enzymes occur as both monomer and homodimer
661401
35200
P54495
recombinant enzyme, about, mass spectrometry, 2 peaks
661401
41000
-
gel filtration
641054
46000
-
monomer, gel filtration
688890
49000
Q4Q1I9
monomer, gel filtration
688890
65000
-
gel filtration
641056
67000
-
gel filtration
641058
67500
-
density gradient centrifugation
641059
70000
P54495
recombinant enzyme, oxidative conditions, PAGE, the wild-type and mutant enzymes occur as both monomer and homodimer
661401
70400
P54495
recombinant enzyme, about, mass spectrometry, 2 peaks
661401
75000
-
recombinant enzyme, gel filtration
661779
86000
Q4Q1I9
dimer, gel filtration
688890
86000
-
dimer, gel filtration
688890
87000
-
HPLC gel filtration
641060
additional information
-
recombinant enzyme, native PAGE
654181
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 47000, SDS-PAGE
?
-
x * 52000, SDS-PAGE
?
-
x * 35000, SDS-PAGE, overexpressed enzyme
?
-
x * 43000, the enzyme may occur as a monomer or dimer, dependent on the protein concentration, SDS-PAGE
?
Q4Q1I9
x * 46000, the enzyme may occur as a monomer or dimer, dependent on the protein concentration, SDS-PAGE
dimer
P0A6V9
homodimer, crystal structure determination
dimer
-
2 * 33500, the recombinant enzyme probably is a dimer, SDS-PAGE
dimer
P54495
2 * 35200, about, mass spectrometry, 2 * 35000, recombinant enzyme, PAGE under oxidative conditions or SDS-PAGE in absence of reductants, the wild-type and mutant enzymes occur as both monomer and homodimer
dimer
-
2 * 36000, alpha2, recombinant enzyme, SDS-PAGE
homodimer
-
2 * 34500, SDS-PAGE
homodimer
-
alpha2, 2 * 24000, SDS-PAGE
homodimer
-
alpha2, 2 * 33000, SDS-PAGE
homodimer
-
alpha2, SDS-PAGE
monomer
-
crystal structure determination
tetramer
P0A4E1
stable form
tetramer
-
unstable form, rapid dissociation to dimers
tetramer
-
SgGlkA is divided into a small alpha/beta domain and a large alpha + beta domain, and it forms a dimer-of-dimer tetrameric configuration
monomer
P54495
1 * 35200, about, mass spectrometry, 1 * 35000, recombinant enzyme, PAGE under reducing conditions or SDS-PAGE in absence of reductants, the wild-type and mutant enzymes occur as both monomer and homodimer
additional information
-
determination of active open and inactive closed enzyme conformation and structure, folding patterns, conformational changes, overview
additional information
-
molecuar structure modeling
additional information
P0A6V9
the active site is located in a deep cleft between the 2 domains of each subunit, monomer and dimer structures, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified recombinant selenomethionine-labeled enzyme free or in complex with D-glucose, hanging drop vapour diffusion method, 0.002 ml enzyme solution containing 6.8 mg/ml protein mixed with 0.004 ml reservoir solution containing 0.1 M Tris-HCl, pH 8.5, 0.2 M MgCl2, and 1.7 M ammonium sulfate for the apo-enzyme or 18.5-20% PEG 6000 with 2 mM D-glucose and 2-3 mM ADP for the glucose-bound enzyme, X-ray diffraction structure determination and analysis at 2.3-2.2 A resolution
P0A6V9
first structures of a glucokinase-glucose complex without activator, of glucokinase-glucose-AMP-PNP and of glucokinase-glucose-AMP-PNP with a bound activator are reported. All structures are extremely similar, thus demonstrating that binding of GK activators does not result in conformational changes of the active protein but in stabilization of the active form of glucokinase
-
purified recombinant hepatic wild-type and deletion mutant enzymes in complex with either D-glucose or the synthetic activator 2-amino-4-fluoro-5-(1-methyl-1H-imidazol-2-ylsulfanyl)-N-thiazol-2-yl-benzamide, hanging drop vapour diffusion method, 10 mg/ml protein in 20 mM Tris-HCl, pH 7.5, 50 mM NaCl, 5 mM Tris(2-carboxyethyl)phosphine hydrochloride, and 20 mM D-glucose, or 0.3 mM compound A, 0.0015-0.003 ml of the solution is mixed with an equal volume of precipitant solution containing 28-30% PEG 1500, 0.1 M HEPES-NaOH, pH 6.0, equilibration against 1 ml precipitant solution, 1 week, crystallization of the free hepatic enzyme by using precipitant solution containing 50 mM NaCl, 1.5-1.6 M ammonium sulfate, and 0.1 M bicine-NaOH, pH 8.7, 1 week, X-ray diffraction structure determination and analysis at 2.3 and 3.4 A resolution, respectively, molecular replacement
-
crystal structures of apo-SgGlkA, SgGlkA in complex with glucose, and SgGlkA in complex with glucose and adenylyl imidodiphosphate (AMPPNP) are reported. SgGlkA is divided into a small alpha/beta domain and a large alpha + beta domain, and it forms a dimer-of-dimer tetrameric configuration
-
crystallized using the sitting-drop vapour-diffusion method. A crystal of SgGlkA in complex with glucose is obtained and diffracted X-rays to 1.84 A resolution
-
crystals of TcGlcK in complex with D-glucose and ADP are obtained by the hanging-drop, vapor-diffusion method, using PEG3350 as precipitant agent and diammonium hydrogen citrate as additive. A complete native dataset is collected to 2.1 A maximum resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
48 h, with glucose and DTT stable, unstable without
641059
40
-
stabilization by D-glucose and glycerol is limited since thermal glucokinase denaturation above 40 C is irreversible even in their presence
721735
55
-
1 min, complete loss of activity
641059
60
-
no loss of activity in 30 min
641058
70
-
about 10% loss of activity in 30 min, presence of 0.01 M glucose + 0.2 M NaCl
641058
70
-
complete loss of activity in 70 min in presence of DTT
641060
70
-
full activity after 10 min
641062
75
-
about 25% loss of activity in 30 min, presence of 0.01 M glucose + 0.2 M NaCl, about 90% loss of activity, presence of 0.01 M glucose absence of NaCl
641058
80
-
quite stable for 120 min
661779
100
-
retains 65% of activity after 10 min
641062
100
-
almost complete inactivation after 5 min
661779
additional information
-
glucose increases thermal stability
641058
additional information
-
glucose or DTT protects against thermal inactivation at 25C
641059
additional information
-
DTT stabilizes at 70C
641060
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
DTT stabilizes at 70C
-
glucose increases thermal stability
-
D-glucose stabilizes the enzyme through a specific, ligand induced intramolecular transition from an open to a closed conformation
-
glycerol increases the stability
-
glucose or DTT protects against thermal inactivation at 25C
-
rapid loss of activity in absence of DTT
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Glycerol
-
glycerol causes large functional changes and increases stability as a result of generalized restructuring of surface water of glucokinase by an indirect mechanism and these changes can occur with minimal perturbation of the protein folding structure and with preservation of the unique cooperative kinetics of the enzyme whereas D-glucose stabilizes the enzyme through a specific, ligand induced intramolecular transition from an open to a closed conformation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
room temperature, 1 mM DTT, 5 mM MgCl2, stable for 1 week , 4C, suspended precipitate in a 60% saturated solution of ammonium sulfate, stable for at least 3 months
-
-20C, stable for 4 weeks
-
-20C, 1 mM DTT, 20-30% glycerol, indefinitely stable
-
room temperature, 1 mM DTT, 5 mM MgCl2, stable for 1 week , 4C, suspended precipitate in a 60% saturated solution of ammonium sulfate, stable for at least 3 months
-
-20C, purified recombinant enzyme, 50 mM Tris-HCl, pH 7.5, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain RB791 by nickel affinity chromatography
P54495
recombinant His-tagged enzyme from strain BL21(DE3) by nickel affinity chromatography
P0A6V9
glutathione S-transferase (GST)-GlkB fusion proteins, wild-type and mutant
Q53Y25
recombinant enzyme
-
recombinant FLAG-tagged hepatic wild-type and mutant enzymes from Escherichia coli strain DH5 alpha by ion exchange and glucosamine affinity chromatography, and gel filtration
-
recombinant N-terminally His6-tagged pancreatic enzyme from Escherichia coli by nickel affinity chromatography to over 90% purity
-
recombinant wild-type and mutant enzymes from Escherichia coli to homogeneity
-
recombinant wild-type and mutant V62M and E300K enzymes as GST-fusion proteins by glutathione affinity chromatography to homogeneity
-
using Ni-NTA chromatography
-
using Ni-NTA chromatography followed by ion-exchange chromatography on a HiTrap Q FF column and gel filtration on a Superdex 200 column
-
recombinant enzyme
Q4Q1I9
recombinant N-terminally His6-tagged hepatic enzyme from Escherichia coli by nickel affinity chromatography to over 90% purity
-
using Ni-NTA chromatography
-
recombinant enzyme from Escherichia coli strain BL21(DE3) by heat treatment and Ni2+ chelating affinity chromatography
-
recombinant soluble His-tagged enzyme from Escherichia coli strain BL21(DE3) by ultracentrifugation, nickel affinity chromatography, and gel filtration to homogeneity
-
His-tagged recombinant TcGlcK is expressed in the Escherichia coli BL21 strain and purified to homogeneity by nickel affinity chromatography
-
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
gene glcK, phylogenetic analysis and tree, functional complementation of enzyme-deficient Escherichia coli strain UE26, overexpression of His-tagged wild-type and mutant enzymes in Escherichia coli strain RB791 as soluble proteins
P54495
expression in Saccharomyces cerevisiae
A1Z0M6
gene glk, expression of His-tagged enzyme in strain BL21(DE3)
P0A6V9
overexpression in Escherichia coli UE79
-
expression of genes nanK, yajF, and ycfX in glk-deficient mutant strain BM5340(DE3)
-
expressed in Escherichia coli as a GST-fusion protein
-
expressed in Escherichia coli as a GST-tagged fusion protein
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
-
expression of hepatic wild-type and mutant enzymes in Escherichia coli strain DH5 alpha as FLAG-tagged proteins
-
expression of the N-terminally His6-tagged pancreatic enzyme in Escherichia coli
-
expression of wild-type and mutant enzymes as GST-fusion proteins
-
expression of wild-type and mutant enzymes in Escherichia coli BL21(DE3)
-
glutathione S-transferase (GST)-GlkB fusion proteins
Q53Y25
expression in Escherichia coli
Q4Q1I9
glcK open reading frame is cloned from Bacillus sphaericus strain C3-41 and then expressed in Escherichia coli
A0SZU9
gene glk is organized in gene clusters, transcriptomic analysis of KT2440 in response to glucose, overview
-
expression of the N-terminally His6-tagged hepatic enzyme in Escherichia coli
-
overexpression in rat hepatocytes
-
expressed in Escherichia coli as a His-tagged fusion protein
-
gene sll0593, DNA and amino acid sequence determination
-
gene TM 1469 or glk, functional expression of the soluble His-tagged in Escherichia coli strain BL21(DE3)
-
gene TM 1469, expression in Escherichia coli strain BL21(DE3)
-
expression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C166A
P54495
site-directed mutagenesis, mutant shows activity similar to the wild-type enzyme
C175A
P54495
site-directed mutagenesis, inactive active site residue mutant
C177A
P54495
site-directed mutagenesis, inactive active site residue mutant
C182A
P54495
site-directed mutagenesis, inactive active site residue mutant
C282A
P54495
site-directed mutagenesis, mutant shows slightly increased enzyme activity compared to the wild-type enzyme, conformational changes different from the wild-type enzyme, overview
C321A
P54495
site-directed mutagenesis, mutant shows 5fold increased enzyme activity compared to the wild-type enzyme, conformational changes different from the wild-type enzyme, overview
A379T
-
kcat(1/sec): 61.2, D-glucose S05 (mM): 12.3, Km (ATP): 0.87 mM, relative inhibition of glucokinase activity through GKRP alone: 17% and GKRP plus 10 microM sorbitol 6-phosphate: 53%
A379V
Q53Y25
mutations is associated with mature-onset diabetes of the young, type 2 (MODY2). Vmax is 65% of maximal activity, Km-value for ATP is 1.5fold higher than wild-type enzyme
A456V
-
mutation leads to increased enzyme activity, associated with hyperinsulinism and hypoglycemia
A456V
-
kcat(1/sec): 65.6, D-glucose S05 (mM): 1.91, Km (ATP): 0.35 mM, relative inhibition of glucokinase activity through GKRP alone: 11% and GKRP plus 10 microM sorbitol 6-phosphate: 28%
C213R
-
kcat(1/sec): 50, D-glucose S05 (mM): 21.6, Km (ATP): 0.89 mM, relative inhibition of glucokinase activity through GKRP alone: 19% and GKRP plus 10 microM sorbitol 6-phosphate: 43%
C233R
Q53Y25
mutations is associated with mature-onset diabetes of the young, type 2 (MODY2). Mutation affects a critical residue of the active center of the enzyme and rendered a protein with undetectable enzymatic activity
C252Y
-
kcat(1/sec): 29.3, D-glucose S05 (mM): 31.6, Km (ATP): 0.75 mM, relative inhibition of glucokinase activity through GKRP alone: 4% and GKRP plus 10 microM sorbitol 6-phosphate: 4%
D158A
-
naturally occurring mutation, activity and kinetics are similar to the wild-type enzyme
D78A/D158A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme
E265K
Q53Y25
mutations is associated with mature-onset diabetes of the young, type 2 (MODY2). Vmax is 86% of maximal activity, Km-value for ATP is 1.13fold lower than wild-type enzyme
E300K
-
site-directed mutagenesis, mutant shows decreased activity and increased thermolability compared to the wild-type enzyme
E339K
-
crystal structure of E339K glucokinase in complex with glucose is shown. This mutation results in a conformational change of His416, spatially interfering with adenosine-triphosphate (ATP) binding
E442K
-
kcat(1/sec): 52.6, D-glucose S05 (mM): 5.24, Km (ATP): 1.5 mM, relative inhibition of glucokinase activity through GKRP alone: 14% and GKRP plus 10 microM sorbitol 6-phosphate: 40%
G227A/D158A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
G68K
-
kcat(1/sec): 43.2, D-glucose S05 (mM): 2.34, Km (ATP): 0.39 mM, relative inhibition of glucokinase activity through GKRP alone: 2% and GKRP plus 10 microM sorbitol 6-phosphate: 20.5%
G68V
-
kcat(1/sec): 62.7, D-glucose S05 (mM): 2.2, Km (ATP): 0.31 mM, relative inhibition of glucokinase activity through GKRP alone: 15% and GKRP plus 10 microM sorbitol 6-phosphate: 32.5%
G72R
-
kcat(1/sec): 29.8, D-glucose S05 (mM): 7.38, Km (ATP): 0.72 mM, relative inhibition of glucokinase activity through GKRP alone: 5% and GKRP plus 10 microM sorbitol 6-phosphate: 6.5%
K102A/D158A
-
site-directed mutagenesis, slightly reduced activity compared to the wild-type enzyme
K140E
-
kcat(1/sec): 40, D-glucose S05 (mM): 10.8, Km (ATP): 0.35 mM, relative inhibition of glucokinase activity through GKRP alone: 9% and GKRP plus 10 microM sorbitol 6-phosphate: 10.5%
K414E
-
kcat(1/sec): 19.9, D-glucose S05 (mM): 5.69, Km (ATP): 1.53 mM, relative inhibition of glucokinase activity through GKRP alone: 13.5% and GKRP plus 10 microM sorbitol 6-phosphate: 49%
K420E
Q53Y25
mutations is associated with mature-onset diabetes of the young, type 2 (MODY2). Vmax is 94% of maximal activity, Km-value for ATP is 1.1fold lower than wild-type enzyme
K90A/D158A
-
site-directed mutagenesis, 2fold increased activity compared to the wild-type enzyme
L146R
-
mutant shows a 100fold reduced kcat and a 40fold increase in [S]0.5 value for D-glucose. Km (ATP) is slightly increased compared to wild-type
M197E
-
kcat(1/sec): 17.7, D-glucose S05 (mM): 41.6, Km (ATP): 0.4 mM, relative inhibition of glucokinase activity through GKRP alone: 13.5% and GKRP plus 10 microM sorbitol 6-phosphate: 18.5%
M197I
-
kcat(1/sec): 58.1, D-glucose S05 (mM): 2.49, Km (ATP): 1.39 mM, relative inhibition of glucokinase activity through GKRP alone: 47% and GKRP plus 10 microM sorbitol 6-phosphate: 59%
M197I/A397T
-
kcat(1/sec): 50.2, D-glucose S05 (mM): 5.81, Km (ATP): 2.71 mM, relative inhibition of glucokinase activity through GKRP alone: 18% and GKRP plus 10 microM sorbitol 6-phosphate: 37%
M197L
-
kcat(1/sec): 62.6, D-glucose S05 (mM): 4.03, Km (ATP): 1.31 mM, relative inhibition of glucokinase activity through GKRP alone: 15% and GKRP plus 10 microM sorbitol 6-phosphate: 37%
N166R
-
increased affinity for glucose and ATP by a factor of 3
N166R-S151-A
-
lowers the KM-value for glucose by a factor of 40 and increases the KM-value for ATP
P417R
-
kcat(1/sec): 48.3, D-glucose S05 (mM): 6.59, Km (ATP): 2.08 mM, relative inhibition of glucokinase activity through GKRP alone: 10% and GKRP plus 10 microM sorbitol 6-phosphate: 39%
S151A
-
lowers the KM-value for glucose by a factor of 26, increases the KM-value for ATP and decreases the KM-value for mannose and fructose
S151C
-
lowers the KM-value for glucose by a factor of 2, increases the KM-value for ATP and decreases the KM-value for mannose and fructose
S151G
-
lowers the KM-value for glucose by a factor of 40, increases the KM-value for ATP and decreases the KM-value for mannose and fructose
S263P
-
kcat(1/sec): 44.6, D-glucose S05 (mM): 9.7, Km (ATP): 0.63 mM, relative inhibition of glucokinase activity through GKRP alone: 19% and GKRP plus 10 microM sorbitol 6-phosphate: 49.5%
S336L
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme
S336L
-
kcat(1/sec): 2.46, D-glucose S05 (mM): 4.75, Km (ATP): 12.6 mM
S411A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
S411L
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme
S64P
-
kcat(1/sec): 83.3, D-glucose S05 (mM): 2.07, Km (ATP): 0.32 mM, relative inhibition of glucokinase activity through GKRP alone: 5% and GKRP plus 10 microM sorbitol 6-phosphate: 4%
S64Y
-
mutation results in an increased affinity for the substrate glucose
S64Y
-
kcat(1/sec): 114, D-glucose S05 (mM): 1.89, Km (ATP): 1.59 mM, relative inhibition of glucokinase activity through GKRP alone: 19% and GKRP plus 10 microM sorbitol 6-phosphate: 15%
T228A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme
T228A/D158A
-
site-directed mutagenesis, very highly reduced activity compared to the wild-type enzyme
T228M
-
mutant shows a 9000fold reduced activity
T65I
-
kcat(1/sec): 22.6, D-glucose S05 (mM): 1.69, Km (ATP): 0.57 mM, relative inhibition of glucokinase activity through GKRP alone: 7.5% and GKRP plus 10 microM sorbitol 6-phosphate: 23%
T82A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme
V182L
Q53Y25
mutations is associated with mature-onset diabetes of the young, type 2 (MODY2). Vmax is 38% of maximal activity, Km-value for ATP is 2.8fold lower than wild-type enzyme
V389L
-
kcat(1/sec): 67.1, D-glucose S05 (mM): 3.45, Km (ATP): 0.76 mM, relative inhibition of glucokinase activity through GKRP alone: 67% and GKRP plus 10 microM sorbitol 6-phosphate: 75%
V452L
-
kcat(1/sec): 122, D-glucose S05 (mM): 2.27, Km (ATP): 0.53 mM, relative inhibition of glucokinase activity through GKRP alone: 19% and GKRP plus 10 microM sorbitol 6-phosphate: 38%
V455M
-
mutation leads to increased enzyme activity, associated with hyperinsulinism and hypoglycemia
V455M
-
kcat(1/sec): 61.8, D-glucose S05 (mM): 3.24, Km (ATP): 0.38 mM, relative inhibition of glucokinase activity through GKRP alone: 26% and GKRP plus 10 microM sorbitol 6-phosphate: 52%
V62A
-
site-directed mutagenesis, mutant shows decreased activity compared to the wild-type enzyme
V62E
-
site-directed mutagenesis, mutant shows decreased activity compared to the wild-type enzyme
V62F
-
site-directed mutagenesis, mutant shows decreased activity compared to the wild-type enzyme
V62K
-
site-directed mutagenesis, mutant shows decreased activity compared to the wild-type enzyme
V62L
-
site-directed mutagenesis, mutant shows similar activity as the wild-type enzyme
V62M
-
site-directed mutagenesis, mutant shows increased activity compared to the wild-type enzyme due to decreased Km for D-glucose, the mutant enzyme is highly temperature-sensitive with a drop in activity at 42.5C
V62M
-
kcat(1/sec): 47.2, D-glucose S05 (mM): 5.9, Km (ATP): 0.52 mM, relative inhibition of glucokinase activity through GKRP alone: 8.5% and GKRP plus 10 microM sorbitol 6-phosphate: 11.5%
V62Q
-
site-directed mutagenesis, mutant shows decreased activity compared to the wild-type enzyme
V62T
-
site-directed mutagenesis, mutant shows decreased activity compared to the wild-type enzyme
V91L
-
kcat(1/sec): 60.6, D-glucose S05 (mM): 1.66, Km (ATP): 0.48 mM, relative inhibition of glucokinase activity through GKRP alone: 6% and GKRP plus 10 microM sorbitol 6-phosphate: 22.5%
W167F/W257F
-
W99 kcat values are markedly lowered compared to wild-type, Km (ATP) increased compared to wild-type, kcat only moderately increased in the presence of glucokinase activator drug
W99R/W167F
-
W257 kcat values are markedly lowered compared to wild-type, Km (ATP) increased compared to wild-type
W99R/W257F
-
W167 kcat values onlye weakly lowered compared to wild-type, Km (ATP) weakly increased compared to wild-type, kcat increased in the presence of glucokinase activator drug
Y214A
-
kcat(1/sec): 117, D-glucose S05 (mM): 1.41, Km (ATP): 0.92 mM, relative inhibition of glucokinase activity through GKRP alone: 24% and GKRP plus 10 microM sorbitol 6-phosphate: 53%
Y214A/V452A
-
kcat(1/sec): 23.1, D-glucose S05 (mM): 0.55, Km (ATP): 1.42 mM, relative inhibition of glucokinase activity through GKRP alone: 11.5% and GKRP plus 10 microM sorbitol 6-phosphate: 20%
Y214C
-
kcat(1/sec): 65.3, D-glucose S05 (mM): 1.35, Km (ATP): 1.08 mM, relative inhibition of glucokinase activity through GKRP alone: 19% and GKRP plus 10 microM sorbitol 6-phosphate: 41%
Y215A
-
kcat(1/sec): 44.7, D-glucose S05 (mM): 2.07, Km (ATP): 0.58 mM, relative inhibition of glucokinase activity through GKRP alone: 6% and GKRP plus 10 microM sorbitol 6-phosphate: 4.5%
D10K
P54495
site-directed mutagenesis, ATP binding site mutant, inactive mutant
additional information
-
construction of an enzyme-deficient glk mutant strain BM5340(DE3), the mutant strain can be complemented by expression of Escherichia coli genes nanK, yajF, and ycfX, which express proteins with 4fold lower glucokinase activity and ambiguous substrate specificities, overview
M298K
-
kcat(1/sec): 37.7, D-glucose S05 (mM): 10.8, Km (ATP): 3.32 mM, relative inhibition of glucokinase activity through GKRP alone: 20% and GKRP plus 10 microM sorbitol 6-phosphate: 44%
additional information
-
construction of N-terminal deletion hepatic enzyme mutants lacking 11 or 15 amino acid residues, respectively
Y61S
Q53Y25
mutations is associated with mature-onset diabetes of the young, type 2 (MODY2). Vmax is 16% of maximal activity, Km-value for ATP is 2.1fold lower than wild-type enzyme
additional information
-
site-specific homologous inactivation of gene glk to construct a mutant strain, activity of the enzyme in isogenic mutants with mutations in the glucose metabolism network, glk mutants exhibit a lower total carbon consumption rate than the parental strain, overview
additional information
-
construction of gene sll0593 deletion mutant, does not respond to glucose level in the growth medium, M1 and M2 show reduced activity in glucose growth medium, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
glucokinase mutations are found only in medically responsive children with congenital hyperinsulinism who are negative for ABCC8 and KCNJ11 mutations
pharmacology
-
enzyme is a target for activator drug design in therapy of type 2 diabetes mellitus