Information on EC 2.7.3.2 - creatine kinase

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The expected taxonomic range for this enzyme is: Metazoa

EC NUMBER
COMMENTARY hide
2.7.3.2
-
RECOMMENDED NAME
GeneOntology No.
creatine kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + creatine = ADP + phosphocreatine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arginine and proline metabolism
-
-
creatine-phosphate biosynthesis
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:creatine N-phosphotransferase
N-Ethylglycocyamine can also act as acceptor.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-15-4
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Antarctic icefish
-
-
Manually annotated by BRENDA team
recombinant mitochondrial isoform
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
tropical fruit bat
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Frog
-
-
-
Manually annotated by BRENDA team
atlantic cod
-
-
Manually annotated by BRENDA team
nurse shark
-
-
Manually annotated by BRENDA team
recombinant cytoplasmic and mitochondrial isoforms
-
-
Manually annotated by BRENDA team
green sunfish
-
-
Manually annotated by BRENDA team
recombinant cytoplasmic isoforms M1, M2, and B
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
rainbow trout
-
-
Manually annotated by BRENDA team
red sea bream
-
-
Manually annotated by BRENDA team
monkey
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Wistar
-
-
Manually annotated by BRENDA team
pacific mackerel
-
-
Manually annotated by BRENDA team
dogfish
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Torpedo californica
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
turtle
-
-
Manually annotated by BRENDA team
syn. Pseudemys scripta elegans, freshwater turtle
-
-
Manually annotated by BRENDA team
trout
-
-
-
Manually annotated by BRENDA team
creatine kinase activity and protein are 20% lower during hibernation than in euthermia, whereas enzyme mRNA is reduced by 70%. Hibernator creatine kinase shows reduced affinity for ATP and creatine. Soluble enzyme from euthermic squirrels is a mix of phosphorylated and dephosphorylated forms. in hibernating animals only phospho-enzyme is detected
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADP + phosphocreatine
ATP + creatine
show the reaction diagram
alpha-(RP)-borano-ADP + phosphocreatine
alpha-(RP)-borano-ATP + creatine
show the reaction diagram
-
the SP-ADPalphaB isomer is a 70fold better substrate for creatine kinase than the RP isomer
-
-
?
alpha-(SP)-borano-ADP + phosphocreatine
alpha-(SP)-borano-ATP + creatine
show the reaction diagram
-
the SP-ADPalphaB isomer is a 70fold better substrate for creatine kinase than the RP isomer
-
-
?
ATP + creatine
ADP + creatine phosphate
show the reaction diagram
ATP + creatine
ADP + phosphocreatine
show the reaction diagram
ATP + cyclocreatine
ADP + phospho-cyclocreatine
show the reaction diagram
ATP + glycocyamine
ADP + glycocyamine phosphate
show the reaction diagram
ATP + N-ethylglycocyamine
ADP + N-ethylglycocyamine phosphate
show the reaction diagram
dADP + phosphocreatine
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + creatine
ADP + creatine phosphate
show the reaction diagram
ATP + creatine
ADP + phosphocreatine
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
MgADP-
-
-
MgATP2-
-
-
NADH
-
activation of cytosolic enzyme in the direction of ATP-formation
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
can substitute for Mg2+
Mn2+
-
required
Zn2+
-
can substitute for Mg2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2Z)-3-butyl-1-phenyl-2-(phenyltellanyl)oct-2-en-1-one
-
organotellurium inhibits creatine kinase activity by two different mechanisms: competition with ADP and oxidation of critical sulfhydryl groups for the functioning of the enzyme
1-anilinonaphthalene-8-sulfonate
unfolding agent
2,3-butadiene
-
complete inhibition, MgATP2- or MgADP- protect the enzyme from inactivation
4,4'-dithiodipyridine
-
-
4-hydroxy-2-nonenal
-
dose-dependent inhibition of creatine kinase, inhibition correlates with 4-hydroxy-2-nonenal adduct formation on specific amino acid residues including the active site residues H66, H191, C283, and H296
4-hydroxy-3-nitrophenylglyoxal
-
complete inactivation, modification of 2 arginine residues per enzyme subunit, inhibition kinetics at pH 8.7, MgATP2- or MgADP- protect the enzyme from inactivation
4-hydroxymercuribenzoic acid
-
-
5,5'-dithiobis(2-nitrobenzoate)
5-(4-([(benzoylphenyl)amino]carbonyl)phenyl)-2-furoic acid
-
35% inhibition, docking energy -49.5 kcal/mol
5-(4-([(biphenyl-4-ylmethyl)amino]carbony)phenyl)-2-furoic acid
-
63% inhibition, docking energy -51.8 kcal/mol
5-(4-benzoylbiphenyl-4-yl)-2-furoic acid
-
; 63% inhibition, docking energy -46.3 kcal/mol
5-(4-[(benzylamino)carbonyl]phenyl)-2-furoic acid
-
20% inhibition, docking energy -47.4 kcal/mol
5-(4-[[(benzoylphenyl)amino]carbonyl]phenyl)-2-furoic acid
-
-
5-(4-[[(biphenyl-4-ylmethyl)amino]carbony]phenyl)-2-furoic acid
-
-
5-[4-[(benzylamino)carbonyl]phenyl]-2-furoic acid
-
-
acetaminophen
-
inhibits creatine kinase in cerebellum and hippocampus, the administration of N-acetylcysteine plus deferoxamine reverses the inhibition of creatine kinase activity
Acrylamide
alpha-P-borano substituted ADP Sp isomer
-
strong competitive inhibitor
Bis-Tris
-
-
bovine serum albumin
-
no influence on enzyme activity
-
Ca2+
-
-
carbon tetrachloride
-
inhibits creatine kinase activity in cerebellum, the administration of N-acetylcysteine plus deferoxamine reverses the inhibition of creatine kinase activity
catechin
-
-
Chromium ADP
-
competitive to MgADP-
Chromium ATP
-
competitive to MgATP2-
-
clozapine
-
inhibition of enzyme in cerebellum and prefrontal cortex after chronic administration
copper metabolism gene MURR1 domain 6
-
0.006 mg is capable of inhibiting the activities of both the MM- and BB-type creatine kinases
-
Creatinine phosphate
Cu2+
-
-
cystine
cystine dimethylester
-
-
ethylmalonic acid
-
accumulation in patients affected by short-chain acyl-CoA dehydrogenase deficiency and other diseases. Ethylmalonic acid inhibits the activity of respiratory chain complexes and also inhibits creatine kinase at concentrations o 1 mM and 5 mM
Fe3+
-
-
formate
guanidine hydrochloride
-
in the absence of added guanidine hydrochloride, MM-CK activity slightly decreases with NaCl concentration up to 4 M, but a dramatic decline is observed above that value, with full inactivation at 4.5 M. When guanidine is added, curves with similar shapes are obtained but NaCl concentrations needed to inactivate the enzyme are shifted towards lower values
Guanidinium chloride
-
inhibitory, in presence of NaCl, increased inhibitory activity. Inactivation by NaCl is due to dissociation of dimeric creatine kinase into its constitutive subunits, and upon monomerization, the protein becomes more susceptible to guanidinium denaturing effect
guanidinium hydrochloride
Guanidinoacetate
-
vitamins E and C prevent the effects of intrastriatal administration of guanidinoacetate on the inhibition of creatine kinase
imidazole
-
-
iodoacetamide
iodoacetic acid
Iodoethane
-
-
L-arginine
-
treatment with single injection or for one week with daily injection of saline or L-Arg plus Nomega-nitro-L-arginine methyl ester or alpha-tocopherol plus ascorbic acid. Total and cytosolic creatine kinase activities are significantly inhibitied by L-arginine adminstration, mitochondrial enzyme activity is not affected. simultaneous injection of Nomega-nitro-L-arginine methyl ester and alpha-tocopherol plus ascorbic acid prevent inhibition
L-isoleucine
-
branched chain alpha-amino acids bind at the active site, competitive inhibition mechanism against substrates phosphocreatine and ADP, inhibition kinetics
L-leucine
-
branched chain alpha-amino acids bind at the active site, competitive inhibition mechanism against substrates phosphocreatine and ADP, inhibition kinetics
L-lysine
-
total and cytosolic creatine kinase activities are significantly inhibited by L-lysine, in contrast to the mitochondrial isoform which is not affected, the inhibitory effect of L-lysine on total creatine kinase activity is totally prevented by reduced glutathione
L-valine
-
branched chain alpha-amino acids bind at the active site, competitive inhibition mechanism against substrates phosphocreatine and ADP, inhibition kinetics
Lactic acid
-
induces dissociation of enzyme dimer and unfolding of the enzyme at 0.8 mM, but no aggregation at 25C or 40C even at high protein concentrations, inactivation kinetics
LiCl
-
inactivation due to subunit dissociation, mechanism
luteolin
-
-
MOPS buffer
-
i.e. 3-(N-morpholino)propane sulfonate
N-ethylmaleimide
-
-
nitrate
nitrite
NO2-
-
-
p-hydroxymercuribenzoate
-
-
Pb2+
-
lead inhibits in vitro the cytosolic and mitochondrial creatine kinase activity at 0.2 mM and that this inhibition is prevented by addition cysteamine to the assay at 0.1 mM and 0.5 mM final concentration
Phenylglyoxal
-
complete inactivation, reacts on arginine residues
phosphate
-
competitive against ATP and phosphocreatine, noncompetitive against ADP and creatine
Pipes buffer
-
i.e. 1,4-piperazine diethanesulfonic acid
quercetin
-
mechanism, role of radicals
SO32-
-
-
SO42-
-
-
sodium barbital
-
slow inactivation of enzyme that can be reversed by dilution. Sodium barbital may compete mainly with creatine, but also with ATP, for inhibition
sulfate
-
competitive against ATP and phosphocreatine, noncompetitive against ADP and creatine
taxifolin
-
-
trans-[RuCl2(3-pyridinecarboxylic acid)4]
-
administration at 180.7 micromol/kg, inhibition of creatine kinase activity in hippocampus, striatum, cerebral cortex, heart and skeletal muscle. No effect on enzyme in vitro
transition state analogue complex
Tris
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ADP
-
activation of creatine kinase and induction of a state 3-like respiration in isolated brain mitochondria, and prevention of H2O2 production obeys the steady-state kinetics of the enzyme to phosphorylate creatine
aripiprazole
-
activation of enzyme in striatum and cerebral cortex after chronic administration at 10 or 20 mg/kg. No effect on enzyme in hippocampus, cerebellum and prefrontal cortex
ATP
-
activation of creatine kinase and induction of a state 3-like respiration in isolated brain mitochondria, and prevention of H2O2 production obeys the steady-state kinetics of the enzyme to phosphorylate creatine
Creatine
-
activation of creatine kinase and induction of a state 3-like respiration in isolated brain mitochondria, and prevention of H2O2 production obeys the steady-state kinetics of the enzyme to phosphorylate creatine
NADH
-
lowers Km for phosphocreatine 3fold
olanzapine
-
activation of enzyme in striatum after chronic administration at 10 mg/kg
trans-[RuCl2(3,4-pyridinedicarboxylic acid)4]
-
administration at 180.7 micromol/kg, increase of creatine kinase activity in hippocampus, striatum, cerebral cortex and heart, but not in skeletal muscle. No effect on enzyme in vitro
trans-[RuCl2(3,5-pyridinedicarboxylic acid)4]
-
administration at 180.7 micromol/kg, increase of creatine kinase activity in hippocampus, striatum, cerebral cortex and heart, but not in skeletal muscle. No effect on enzyme in vitro
additional information
-
increase of enzymatic activity post-exercise
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.027 - 0.33
ADP
1
alpha-(RP)-borano substituted ADP
-
-
0.008
alpha-(SP)-borano substituted ADP
-
-
0.11 - 20
ATP
0.35 - 167
Creatine
0.23 - 50
creatine phosphate
0.015 - 1.2
MgADP-
0.042 - 10.3
MgATP2-
0.51 - 8.97
phosphocreatine
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
78.3 - 483.3
ADP
0.06
alpha-(RP)-borano substituted ADP
Oryctolagus cuniculus
-
-
0.03
alpha-(SP)-borano substituted ADP
Oryctolagus cuniculus
-
-
36.4 - 215
ATP
0.08 - 417
Creatine
1.5 - 35.2
cyclocreatine
0.08 - 148
MgATP2-
0.55 - 14.5
N-ethylglycocyamine
78.3 - 483.3
phosphocreatine
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2.37 - 16.46
(2Z)-3-butyl-1-phenyl-2-(phenyltellanyl)oct-2-en-1-one
0.025
5-(4-([(benzoylphenyl)amino]carbonyl)phenyl)-2-furoic acid
0.049
alpha-P-borano substituted ADP Sp isomer
-
-
10 - 21
L-isoleucine
16 - 22
L-leucine
14 - 23
L-valine
1.22
SDS
-
in 5 mM glycine-NaOH (pH 9.0), at 25C
additional information
additional information
-
inhibition kinetics with 4-hydroxy-3-nitrophenylglyoxal, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15
Zn2+
Oryctolagus cuniculus
-
at 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.99
-
crude homogenate
15
-
synthesis of phosphocreatine
22
-
mutant Trp to Phe
26
-
mutant Trp to Asn
26.8
-
mutant Tyr to Asn
28.8
-
mutant Tyr to His
29.6
-
mutant Trp to Cys
31.8
-
wild-type
32
-
mutant Trp to His
36.4
-
mutant Trp to Tyr
43.48
-
enzyme from embryonic stem cell-derived cardiomyocytes, pH 6.5, 37C
43.7
-
mutant W264C
46.5
-
mutant L115D
49.5
-
synthesis of ATP
50.25
-
enzyme from neonatal cardiomyocytes, pH 6.5, 37C
52
-
mutant D54G; mutant enzyme D54G
62.3
-
mutant W264Y
70.2
-
wild-type
71.2
-
mutant Tyr to Trp
94.4
-
mutant L121D
148
-
mutant V72A, 25C
205.1
-
after 68.6fold purification
206
-
purified cytosolic isozyme
210
-
oxidized form of creatine kinase
240
-
purified mitochondrial isozyme
245.5
-
wild-type enzyme
246
-
wild-type
250
-
30C, pH 7.0
256
-
mutant C74M, 25C
258
-
mutant C74L, 25C
263
-
mutant V75A, 25C
266
-
mutant C74S, 25C
272
-
mutant A76G, 25C
274.9
-
reduced form of creatine kinase
276
-
wild-type
278
-
mutant C74A, 25C
299
-
mutant L110D
345
-
isoform CK1, pH 6.7
410
-
30C
511
-
isoform CK2, pH 6.7
8208
-
mutant G73A, 25C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 6.5
-
synthesis of MgATP2-
6.3
-
synthesis of MgATP2-
6.5
-
enzyme from neonatal cardiomyocytes
6.7
-
synthesis of MgATP2-
6.8
native enzyme in solution
7 - 7.5
-
-
7 - 9
-
assay at
7
-
enzyme from embryonic stem cell-derived cardiomyocytes
7 - 9
-
assay at
7 - 7.5
7.4
-
assay at
7.5 - 9
7.5 - 9
8
-
synthesis of phosphocreatine
8 - 8.3
-
synthesis of phosphocreatine
8
-
assay at
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42 - 45
-
synthesis of ATP
42
-
synthesis of phosphocreatine
45
-
both for enzyme from embryonic stem cell-derived cardiomyocytes and from neonatal cardiomyocytes
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 25
optimal temperature