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Information on EC 3.1.1.7 - acetylcholinesterase and Organism(s) Mus musculus and UniProt Accession P21836
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3.1.1.7 acetylcholinesteraseIUBMB Comments
Acts on a variety of acetic esters; also catalyses transacetylations.
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Word Map
- 3.1.1.7
-
cholinergic
- alzheimer
- nerve
- butyrylcholinesterase
-
organophosphate
-
pesticide
- hippocampus
-
neurotoxicity
- dementia
- erythrocyte
- deficit
-
organophosphorus
-
insecticide
-
muscarinic
- donepezil
- synaptic
-
neuroprotective
- cerebral
- acetyltransferase
- fiber
-
maze
- cortical
-
innervation
-
poison
- cholinesterases
-
nicotinic
-
neurotransmitter
- neuromuscular
- neurodegenerative
- atropine
- axon
- oxime
- carbamate
-
chat
-
histochemistry
-
amyloid
-
morris
-
neurochemical
-
monoamine
- synapses
-
intoxication
- chlorpyrifos
- striatum
-
neurotransmission
-
postsynaptic
- forebrain
- carboxylesterase
-
antidote
-
parasympathetic
- biotechnology
- synthesis
- analysis
- pharmacology
- medicine
- diagnostics
-
anticholinergic
- environmental protection
- drug development
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
ache, acetylcholinesterase, acetylcholine esterase, acetyl cholinesterase, hache, eeache, ache1, huache, tcache, membrane-bound acetylcholinesterase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AcCholE
-
-
-
-
acetyl beta-methylcholinesterase
-
-
-
-
acetylcholine esterase
-
-
-
-
acetylcholine hydrolase
-
-
-
-
acetylthiocholinesterase
-
-
-
-
AChE
choline esterase I
-
-
-
-
cholinesterase
-
-
-
-
esterase, acetyl choline
-
-
-
-
true cholinesterase
-
-
-
-
AChE
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acetylcholine + H2O = choline + acetate
formation of the trigonal bipyramidal transition state
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of carboxylic ester
-
-
-
-
transacetylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
acetylcholine acetylhydrolase
Acts on a variety of acetic esters; also catalyses transacetylations.
CAS REGISTRY NUMBER
COMMENTARY
9000-81-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
alkyl methylphosphonfluoridate + H2O
?
-
oxime-assisted catalysis of organophosphates by AChE, mechanism, reaction system, overview
-
-
?
S-acetylthiocholine + H2O
acetate + thiocholine
-
detection with 5,5'-dithio-bis-2-nitrobenzoic acid, i.e. DTNB
-
-
?
S-acetylthiocholine iodide + H2O
acetate + thiocholine iodide
-
detection with 5,5'-dithio-bis-2-nitrobenzoic acid, i.e. DTNB
-
-
?
acetylcholine + H2O
acetate + choline
-
acetylcholine protects cardiomyocytes from prolonged hypoxia through activation of the PI3K/Akt/HIF-1alpha/VEGF pathway and that cardiomyocyte-derived VEGF promotes angiogenesis in a paracrine fashion
-
-
?
acetylcholine + H2O
choline + acetate
-
esteratic and anionic subsites act together to achieve substrate binding specificity
-
?
additional information
?
-
substrate and product trafficking through the active center gorge of the enzyme analyzed by crystallography and equilibrium binding, binding structures, overview
-
-
?
additional information
?
-
-
substrate and product trafficking through the active center gorge of the enzyme analyzed by crystallography and equilibrium binding, binding structures, overview
-
-
?
additional information
?
-
-
the enzyme is involved in the morphogenetic processes of neuronal and non-neuronal tissues
-
-
?
additional information
?
-
-
brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway, overview
-
-
?
additional information
?
-
-
presenilin 1, PS1, is required for enzyme activity in the brain, PS1/A246E transgenic mice have altered AChE activity in several regions also vulnerable in Alzheimer pathology, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetylcholine + H2O
acetate + choline
-
acetylcholine protects cardiomyocytes from prolonged hypoxia through activation of the PI3K/Akt/HIF-1alpha/VEGF pathway and that cardiomyocyte-derived VEGF promotes angiogenesis in a paracrine fashion
-
-
?
additional information
?
-
-
the enzyme is involved in the morphogenetic processes of neuronal and non-neuronal tissues
-
-
?
additional information
?
-
-
brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway, overview
-
-
?
additional information
?
-
-
presenilin 1, PS1, is required for enzyme activity in the brain, PS1/A246E transgenic mice have altered AChE activity in several regions also vulnerable in Alzheimer pathology, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aluminium chloride
-
activates the enzyme in vitro and in vivo after oral treatment
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
bambuterol
a specific and stereoselective inhibitor of butyrylcholinesterase, which is about 8000times faster inhibited than acetylcholinesterase. AChE wild-type enzyme, and mutants F297I/Y337A and F295L/F297I/Y337A show a deviation from linearity, either enzymes are inhibited by racemate or enantiomers, indicating the presence of reversible enzyme-inhibitor complex, overview
fasciculin
binds at the mouth of the gorge, decreases the mobility of reporter groups attached to L76C and Y124C, increases the mobility of reporter groups attached to E81C and E84C
-
huperzine
binds at the base of the active site gorge, has no effect on the mobility of reporter groups attached to L76C and Y124C, increases the mobility of reporter groups attached to E81C and E84C
m-(N,N,N-trimethylammonio)-trifluoroacetophenone
binding structure analysis
methamidophos
an organophosphorous-based insecticide, binding structure, overview
TFK+
analysis of the inhibition mechanism by ab initio quantum mechanical/molecular mechanical approach and classical molecular dynamics simulations, overview
TFK0
analysis of the inhibition mechanism by ab initio quantum mechanical/molecular mechanical approach and classical molecular dynamics simulations, overview
VX (nerve agent)
i.e. O-ethyl S-2-isopropylaminoethyl methylphosphonothiolate, nerve agent, binding structure, overview
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
E2020, acetylcholinesterase inhibitor used in treatment of Alzheimer's diaease, inhibition kinetics
2,2-dichlorovinyl dimethyl phosphate
-
i.e. DDVP, reversible, detailed kinetic analysis
2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride
-
i.e. 2-PAM, reversible, detailed kinetic analysis
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
-
i.e. HI-6, reversible, detailed kinetic analysis
4-O-methylhonokiol
-
isolated from ethanol extract of Magnolia officinalis. 4-O-methylhonokiol also dose-dependently attenuates the scopolamine-induced increase of AChE activity in the cortex and hippocampus of mice
aflatoxin B1
-
50% inhibition at 0.031 mM by increase of Km-value and decrease of vmax-value. Partial recativation by 2-aldoxime, i.e. 2-PAM, pyridin-2-aldoxime 1-methoiodide
Insulin
-
AChE activity in detergent soluble fraction of scopolamine amnesic mice is inhibited by donepezil, insulin and melatonin with varying extent in different brain regions, whereas AChE activity in salt soluble fraction is not much affected, overview
-
Melatonin
-
AChE activity in detergent soluble fraction of scopolamine amnesic mice is inhibited by donepezil, insulin and melatonin with varying extent in different brain regions, whereas AChE activity in salt soluble fraction is not much affected, overview
methyl (3-{4-[({[5-(dimethylamino)naphthalen-1-yl]sulfonyl}amino)methyl]-1H-1,2,3-triazol-1-yl}propyl)phosphonofluoridate
-
-
methyl (3-{4-[({[6-(diethylamino)-2-oxo-2H-chromen-3-yl]carbonyl}amino)methyl]-1H-1,2,3-triazol-1-yl}propyl)phosphonofluoridate
-
-
methyl (4-{4-[({[5-(dimethylamino)naphthalen-1-yl]sulfonyl}amino)methyl]-1H-1,2,3-triazol-1-yl}butyl)phosphonofluoridate
-
-
methyl (4-{4-[({[6-(diethylamino)-2-oxo-2H-chromen-3-yl]carbonyl}amino)methyl]-1H-1,2,3-triazol-1-yl}butyl)phosphonofluoridate
-
-
methyl paraoxon
-
reversible binding to a site on acetylcholinesterase distinct from the active site reduces their subsequent capacity to phosphorylate the active site, probably by steric hindrance or allosteric modification of the active site
methyl [3-(4-{[(4-{(E)-[4-(dimethylamino)phenyl]diazenyl}benzoyl)amino]methyl}-1H-1,2,3-triazol-1-yl)propyl]phosphonofluoridate
-
-
methyl [3-(4-{[(pyren-2-ylsulfonyl)amino]methyl}-1H-1,2,3-triazol-1-yl)propyl]phosphonofluoridate
-
-
methyl [4-(4-{[(4-{(E)-[4-(dimethylamino)phenyl]diazenyl}benzoyl)amino]methyl}-1H-1,2,3-triazol-1-yl)butyl]phosphonofluoridate
-
-
methyl [4-(4-{[(pyren-2-ylsulfonyl)amino]methyl}-1H-1,2,3-triazol-1-yl)butyl]phosphonofluoridate
-
-
methyl {3-[4-({[(6-methoxy-2-oxo-2H-chromen-3-yl)carbonyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propyl}phosphonofluoridate
-
-
methyl {4-[4-({[(6-methoxy-2-oxo-2H-chromen-3-yl)carbonyl]amino}methyl)-1H-1,2,3-triazol-1-yl]butyl}phosphonofluoridate
-
-
muscarine
-
treatment with 0.01 mM muscarine leads to a 20% decrease in enzyme activity in SN-56 cells
O-O-dimethyl-O-(2,2-dichlorovinyl)phosphate
-
phosphorylates the active site serine
RP cycloheptyl methylphosphonyl thiocholine
-
phosphonylates the enzyme, wild-type enzyme and mutant enzymes can only poorly be reactivated by 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide
RP-3,3-dimethylbutyl methylphosphonyl thiocholine
-
phosphonylates the enzyme, wild-type enzyme and mutant enzymes can only poorly be reactivated by 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide
RP-isopropyl methylphosphonyl thiocholine
-
phosphonylates the enzyme, wild-type enzyme and mutant enzymes can be partially reactivated by 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide
SP-3,3-dimethylbutyl methylphosphonyl thiocholine
-
phosphonylates the enzyme, wild-type enzyme and mutant enzymes can be partially reactivated by 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide
SP-cycloheptyl methylphosphonyl thiocholine
-
phosphonylates the enzyme, wild-type enzyme and mutant enzymes can be partially reactivated by 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide
SP-isopropyl methylphosphonyl thiocholine
-
phosphonylates the enzyme, wild-type enzyme and mutant enzymes can be partially reactivated by 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide
fenamiphos
an organophosphorous-based insecticide, binding structure, overview
BW284c51
-
i.e. 1,5-bis(4-allyldimethyl-ammoniumphenyl)pentane-3-one dibromide, specific inhibition of AChE
donepezil
-
AChE activity in detergent soluble fraction of scopolamine amnesic mice is inhibited by donepezil, insulin and melatonin with varying extent in different brain regions, whereas AChE activity in salt soluble fraction is not much affected, overview
donepezil
-
donepezil concomitantly elevates VEGF expression in intracardiac endothelial cells of wild-type and alpha7 KO mice and further increases choline acetyltransferase protein expression, which is critical for acetylcholine synthesis in endothelial cells
fasciculin
-
inhibits catalysis peripherally by sealing the mouth of the active center gorge
-
galanthamine
-
a competitive and reversible, specific inhibitor, crosses the blood brain barrier, significantly increases brain cholinergic network activity
paraoxon
-
26% inhibition at 0.0000001 mM, reversible binding to a site on acetylcholinesterase distinct from the active site reduces their subsequent capacity to phosphorylate the active site
additional information
oxime-based reactivators, such as [(E)-[1-[(4-carbamoylpyridin-1-ium-1-yl)methoxymethyl]pyridin-2-ylidene]methyl]-oxoazanium dichloride, i.e. HI-6, and 1,7-heptylene-bis-N,N0-2-pyridiniumaldoxime dichloride, i.e. Ortho-7, restore the organophosphate-inhibited enzymatic activity by cleaving the phosphorous conjugate, overview. Flipping of the His447 imidazole ring allows the formation of a hydrogen bonding network among the Glu334-His447-Ortho-7 triad, which presumably deprotonates the Ortho-7 oxime hydroxyl group, increases the nucleophilicity of the oxime group, and leads to cleavage of the phosphorous conjugate. Binding structure determination and analysis, higher reactivation rate of HI-6 than Ortho-7, overview
-
additional information
-
oxime-based reactivators, such as [(E)-[1-[(4-carbamoylpyridin-1-ium-1-yl)methoxymethyl]pyridin-2-ylidene]methyl]-oxoazanium dichloride, i.e. HI-6, and 1,7-heptylene-bis-N,N0-2-pyridiniumaldoxime dichloride, i.e. Ortho-7, restore the organophosphate-inhibited enzymatic activity by cleaving the phosphorous conjugate, overview. Flipping of the His447 imidazole ring allows the formation of a hydrogen bonding network among the Glu334-His447-Ortho-7 triad, which presumably deprotonates the Ortho-7 oxime hydroxyl group, increases the nucleophilicity of the oxime group, and leads to cleavage of the phosphorous conjugate. Binding structure determination and analysis, higher reactivation rate of HI-6 than Ortho-7, overview
-
additional information
-
organophosphate inhibitor binding and active site gorge structure, oveview, nucleophilic oximes, i.e. bis-quarternary oximes, aldoximes, and hydroxamates, act as reactivators of the inhibited enzyme and are of therapeutic use, overview
-
additional information
-
blueberry polyphenols, as gallic acid equivalents, directly inhibit AChE to 64-66% reduced activity of the detergent soluble and the salt soluble enzyme, respectively
-
additional information
-
chromophore-linked fluorophosphonate inhibitors show bimolecular inhibition constants ranging from 0.3 * 105 M/min to 10.4 * 105 M/min
-
additional information
-
inhibitory effect on AChE of the ethanol extract of Magnolia officinalis, overview
-
additional information
-
oximes poorly reactivate tabun-inhibited AChE. In silico pharmacophore model for binding affinity of tabun-inhibited AChE from a set of 11 oximes, 9 of which show binding to the inhibited enzyme, overview. Stereoelectronic profiles and three-dimensional quantitative structure-activity relationship pharmacophores using ab initio quantum chemical and pharmacophore generation methods, detailed overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
aluminium lactate
-
activates the enzyme in vitro and in vivo after oral treatment
presenilin 1
-
PS1, required for enzyme activity in the brain, overview. PS1-deficient mice show upregulation of AChE activity in major cholinergic cell nuclei and in cortical and thalamic regions responsible for selective attention and visuomotor coordination, as well as limbic structures with related regions involved in cognition, arousal, emotion, and plasticit, overview
-
Scopolamine
-
induces and increase of AChE activity in the cortex and hippocampus of mice
Carbachol
-
0.01 mM carbachol leads to a significant increase in enzyme activity in SH-SY5Y cells
Carbachol
-
a 15 min pretreatment of the cells at 37°C with 0.01 mM atropine completely ablates the carbachol-induced increase in enzyme activity
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.46
acetylthiocholine
-
pH 7.5, 37°C, addition of aluminium lactate during measurement of activity
0.61
acetylthiocholine
-
pH 7.5, 37°C, addition of AlCl3 during measurement of activity
1
acetylthiocholine
-
pH 7.5, 37°C, after treatment with aluminium lactate for 3 months
2.5
acetylthiocholine
-
pH 7.5, 37°C addition of sodium lactate during measurement of activity
2.5
acetylthiocholine
-
pH 7.5, 37°C, addition of NaCl during measurement of activity
2.5
acetylthiocholine
-
pH 7.5, 37°C, after treatment with sodium lactate for 3 months
additional information
additional information
ligand binding kinetics, overview
-
additional information
additional information
-
ligand binding kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.023
4-ketoamyltrimethylammonium
pH 7.0, 22°C, recombinant wild-type enzyme
0.0000004 - 0.0087
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
0.046 - 0.36
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
0.0000004
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, Y337A mutant
0.0000005
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, Y337F mutant
0.0000022
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, wild-type enzyme
0.00002
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, Y124Q mutant
0.00002
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, Y72N mutant
0.000027
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, F295L mutant
0.00007
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, F297I mutant
0.00069
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, W86A mutant
0.0032
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, W286A mutant
0.0051
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, D74N mutant
0.0087
(R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
-
pH 8, 25°C, Y72N/Y124N/W286R mutant
0.15
2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride
-
pH 7.0, 25°C, wild-type
0.28
2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride
-
pH 7.0, 25°C, mutant Y72N/Y124Q/W286A
0.59
2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride
-
pH 7.0, 25°C, mutant Y337A
0.65
2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride
-
pH 7.0, 25°C, mutant F295L/Y337A
1.7
2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride
-
pH 7.0, 25°C, mutant F297I/Y337A
0.046
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
-
pH 7.0, 25°C, wild-type
0.087
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
-
pH 7.0, 25°C, mutant Y337A
0.11
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
-
pH 7.0, 25°C, mutant F295L/Y337A
0.18
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
-
pH 7.0, 25°C, mutant F297I/Y337A
0.36
4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride
-
pH 7.0, 25°C, mutant Y72N/Y124Q/W286A
additional information
additional information
inhibition kinetics, wild-type and mutant enzymes, overview
-
additional information
additional information
-
inhibition kinetics, wild-type and mutant enzymes, overview
-
additional information
additional information
inhibition kinetics of wild-type and knockout mutant enzyme
-
additional information
additional information
-
inhibition kinetics of wild-type and knockout mutant enzyme
-
additional information
additional information
-
inhibition rate constants, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
enzyme activity in wild-type and PS1/A246E transgenic mice, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
first enzyme appearance in the developing cervical loops of the enamel organ, but does not appear in the enamel knot, overview
-
dental, inner enamel epithelium except cervical-loop area in inscisors and neonatal mice, not in the outer enamel epithelium, temporospatial localization of enzyme activity in the dental epithelium during mouse tooth development, overview
-
inner enamel epithelium except cervical-loop area in inscisors and neonatal mice, temporospatial localization of enzyme activity in the dental epithelium during mouse tooth development, AChE localization in mandibular and maxillary tooth buds, also in the enamel-free area, but weakly in the dental papilla and its neural elements, and not in the outer enamel epithelium, stellate reticulum, and ameloblasts, overview
additional information
-
medial septum, vertical diagonal band,substantia inominata, eye field, posterior parietal and visual cortices, posterior thalamic and lateral geniculate nuclei, hippocampal formation and amygdala, midline, periventricular, reticular thalamic nuclei, and lateral prefrontal, agranular insular cortices
additional information
-
no enzyme activity in the secretory and maturation periods of ameloblasts, and not in the outer enamel epithelium, and stellate reticulum
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
enzyme anchorage in the membrane is established via the proline rich membrane anchor transmembrane protein
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ACES_MOUSE
614
0
68169
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
primary and tertiary structure determination and anaylsis, the active site gorge forms asterically confined environment
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with inhibitors, nerve agents and organophosphorous-based insecticides, in aged and non-aged forms, the non-aged complexes are generated by crystal soaking methods, by slow equilibration of crystals in X-buffer composed of 28% v/v PEG monomethyl ether 750, and 100 mM HEPES, pH 7.0, prior to data collection, X-buffer is supplemented with the appropriate organophosphorous compound at a concentration of 10 mM for sarin, VX, and diisopropyl fluorophosphate and 100 mM for methamidophos and fenamifos, the solution is subsequently added to the equilibrated crystals in several portions during different periods, aged forms establish during several weeks, X-ray diffraction structure determination and anaylsis at 2.5-2.9 A resolution, modelling
in complex with tabun, prior and after intramolecular dealkylation or deamidation reaction caused by tabun and called aging. Nonaged tabun conjugate induces a structural change at H447 that uncouples the catalytic triad. In aged tabun conjugate, side chains of H447 and F338 are reversed to the conformation of the apo structure of enzyme
purified recombinant enzyme bound to inhibitor fenamiphos and oxime-based reactivators [(E)-[1-[(4-carbamoylpyridin-1-ium-1-yl)methoxymethyl]pyridin-2-ylidene]methyl]-oxoazanium dichloride, and 1,7-heptylene-bis-N,N0-2-pyridiniumaldoxime dichloride, mixture of 0.001 ml 20 mg/ml AChE with 0.001 ml well solution containing 28% PEG750MME and 0.1mM HEPES, pH 7.0-7.2, saturated with fenamiphos, for 22-25 h, crystals are soakened in inhibitor solution, X-ray diffraction structure determination and analysis at 2.4-2.7 A resolution
purified wild-type enzyme and mutant S203A in complex with substrates acetylcholine, acetylthiocholine, succinyldicholine, and butyrylthiocholine, and two nonhydrolyzable substrate analogues (m-N,N,N-trimethylammonio)-trifluoroacetophenone and 4-ketoamyltrimethylammonium, by hanging drop vapor diffusion at 4°C, using a protein-to-well solution ratio of 1:1, with well solution containing 2532% v/v P550MME or P600 in either 60-100 mM HEPES or sodium acetate, pH 6.5-pH 8.0, he TMTFA-mAChE complex is formed in solution using apo-mAChE at 5.0 mg/ml, and a 3-fold molar excess of the ligand over the enzyme, concentrated prior to crystallization, the other seven complexes are generated by crystal soaking, carried out at 4 °C in 0.02 ml sitting drops made of well solution supplemented with the 250 mM ligand and polyethylene glycol up to 35%, X-ray diffraction structure determination and anaylsis at 2.05-2.65 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E81C
reporter group 5-((((2-acetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid attached to cysteine
E84C
reporter group 5-((((2-acetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid attached to cysteine
F295L/Y337A
F296L/F297I/Y337A
site-directed mutagenesis, the mutant shows a 14fold decreased inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
F297I/Y337A
H447I
inhibitor TFK+ binding to the H447I mutant proceeds with a different reaction mechanism from the wild-type enzyme. A water molecule takes over the role of His447 and participates in the bond breaking and forming as a charge relayer. Unlike in the wild-type mAChE case, Glu334, a conserved residue from the catalytic triad, acts as a catalytic base in the reaction
L76C
reporter group 5-((((2-acetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid attached to cysteine
S203A
site-directed mutagenesis of the catalytic site residue, inactive mutant
Y124C
reporter group 5-((((2-acetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid attached to cysteine
Y124Q
site-directed mutagenesis, the mutant shows an altered inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
Y337A
site-directed mutagenesis, the mutant shows an altered inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
Y72N/Y124Q/Y337A
site-directed mutagenesis, the mutant shows an altered inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
A262C
E84C
-
4fold increased Km, 2fold increase in Kd for edrophonium binding, 18fold increase for 1,5-bis(4-allyldimethylammoniumphenyl)-pentan-3-one dibromide binding
F295L
F295L/F297I/Y337A
-
mutant enzyme can be partially reactivated after phosphonylation
F295L/Y337A
F297I
H287C
W286A
Y124C
Y124Q
Y337A
Y337A/F338A
Y72N
additional information
F295L/Y337A
site-directed mutagenesis, the mutant an altered inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
F295L/Y337A
site-directed mutagenesis, the mutant shows a 13fold increased inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
F297I/Y337A
increased inhibition by RP-cycloheptyl methylphosphonyl thiocholine
F297I/Y337A
site-directed mutagenesis, the mutant shows an altered inhibition rate with inhibitor bambuterol compared to the wild-type enzyme
A262C
-
kinetics similar to wild-type enzyme, association and dissociation rate of fasciculin similar to wild type enzyme
F295L
-
analysis of inhibition kinetics for 2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride, 4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride, and 2,2-dichlorovinyl dimethyl phosphate
F295L
-
the mutant shows enhanced reactivation rate by the oximes HI-6 and 2-PAM compared to the wild-type enzyme
F295L/Y337A
-
the mutant shows 120fold enhanced reactivation rate by the oximes HI-6 and 2-PAM compared to the wild-type enzyme
F297I
-
analysis of inhibition kinetics for 2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride, 4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride, and 2,2-dichlorovinyl dimethyl phosphate
F297I
-
the mutant shows enhanced reactivation rate by the oximes HI-6 and 2-PAM compared to the wild-type enzyme
H287C
-
kinetics similar to wild-type enzyme, association and dissociation rate of fasciculin similar to wild type enzyme
W286A
-
analysis of inhibition kinetics for 2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride, 4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride, and 2,2-dichlorovinyl dimethyl phosphate
Y124C
-
kinetics similar to wild-type enzyme, association and dissociation rate of fasciculin similar to wild type enzyme
Y124Q
-
analysis of inhibition kinetics for 2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride, 4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride, and 2,2-dichlorovinyl dimethyl phosphate
Y337A
-
reactivation of mutant enzyme after phosphonylation with RP-3,3-dimethylbutyl methylphosphonyl thiocholine with 1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4''-carbamoyl-1''-pyridinium)-2-oxapropane dichloride or 2-(hydroxyiminomethyl)-1-methylpyridinium iodide is better than reactivation of wild-type enzyme
Y337A
-
analysis of inhibition kinetics for 2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride, 4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride, and 2,2-dichlorovinyl dimethyl phosphate
Y337A
-
the mutant shows enhanced reactivation rate by the oximes HI-6 and 2-PAM compared to the wild-type enzyme
Y337A/F338A
-
the mutant shows enhanced reactivation rate by the oximes HI-6 and 2-PAM compared to the wild-type enzyme
Y72N
-
analysis of inhibition kinetics for 2-((Z)-(hydroxyimino)methyl)-1-methylpyridinium chloride, 4-(aminocarbonyl)-1-(((2-((Z)-(hydroxyimino)methyl)pyridinium-1-yl)methoxy)methyl)pyridinium dichloride, and 2,2-dichlorovinyl dimethyl phosphate
additional information
-
neuromuscular transmission during repetitive nerve stimulation is severely depressed in the AChE knockout mice, AChE deficiency phenotype, overview
additional information
-
donepezil accelerates angiogenesis even in alpha7 KO mice with hindlimb ischemia. alpha7 KO mice phenotype, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant soluble wild-type and mutant enzymes from HEK-293 cells by by affinity chromatography with elution using either propidium diiodide or SCh dichloride, followed by dialysis
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
AChE, when conjugated with organophosphorous compounds, is employed as a template for socalled click-chemistry, freeze-frame synthesis of nucleophilic reactivating agents that could potentially prove useful in AChE reactivation at the target site as well as in catalytic scavenging of organophosphates in plasma, overview
medicine
-
chronic administration of tea polyphenol significantly reverses scopolamine-induced retention deficits in both step-through passive avoidance and spontaneous alternation behavioural tasks. Additionally, tea polyphenol inhibits enzyme activity and may be useful in treatment of Alzheimers disease
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bourne, Y.; Taylor, P.; Bougis, P.E.; Marchot, P.
Crystal structure of mouse acetylcholinesterase. A peripheral site-occluding loop in a tetrameric assembly
J. Biol. Chem.
274
2963-2970
1999
Mus musculus
Marchot, P.; Ravelli, R.B.G.; Raves, M.L.; Bourne, Y.; Vellom, D.C.; Kanter, J.; Camp, S.; Sussman, J.L.; Taylor, P.
Soluble monomeric acetylcholinesterase from mouse: expression, purification, and crystallization in complex with fasciculin
Protein Sci.
5
672-679
1996
Mus musculus
Gomez, J.L.; Moral-Naranjo, M.T.; Compoy, F.J.; Vidal, C.J.
Characterization of acetylcholinesterase and butyrylcholinesterase forms in normal and dystrophic Lama2dy mouse heart
J. Neurosci. Res.
56
295-306
1999
Mus musculus
Kovarik, Z.; Radic, Z.; Berman, H.A.; Simeon-Rudolf, V.; Reiner, E.; Taylor, P.
Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates
Biochem. J.
373
33-40
2003
Mus musculus (P21836), Mus musculus
Kovarik, Z.; Radic, Z.; Berman, H.A.; Simeon-Rudolf, V.; Reiner, E.; Taylor, P.
Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugates
Biochemistry
43
3222-3229
2004
Mus musculus
Zatta, P.; Ibn-Lkhayat-Idrissi, M.; Zambenedetti, P.; Kilyen, M.; Kiss, T.
In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase
Brain Res. Bull.
59
41-45
2002
Mus musculus
Saxena, A.; Fedorko, J.M.; Vinayaka, C.R.; Medhekar, R.; Radic, Z.; Taylor, P.; Lockridge, O.; Doctor, B.P.
Aromatic amino-acid residues at the active and peripheral anionic sites control the binding of E2020 (Aricept) to cholinesterases
Eur. J. Biochem.
270
4447-4458
2003
Mus musculus, Tetronarce californica
Gomez, J.L.; Nieto-Ceron, S.; Campoy, F.J.; Munoz-Delgado, E.; Vidal, C.J.
Purification and properties of hydrophilic dimers of acetylcholinesterase from mouse erythrocytes
Int. J. Biochem. Cell Biol.
35
1109-1118
2003
Mus musculus
Kua, J.; Zhang, Y.; McCammon, J.A.
Studying enzyme binding specificity in acetylcholinesterase using a combined molecular dynamics and multiple docking approach
J. Am. Chem. Soc.
124
8260-8267
2002
Mus musculus
Boyd, A.E.; Marnett, A.B.; Wong, L.; Taylor, P.
Probing the active center gorge of acetylcholinesterase by fluorophores linked to substituted cysteines
J. Biol. Chem.
275
22401-22408
2000
Mus musculus
Shi, J.; Boyd, A.E.; Radic, Z.; Taylor, P.
Reversibly bound and covalently attached ligands induce conformational changes in the omega loop, Cys69-Cys96, of mouse acetylcholinesterase
J. Biol. Chem.
276
42196-42204
2001
Mus musculus
Shi, J.; Tai, K.; McCammon, J.A.; Taylor, P.; Johnson, D.A.
Nanosecond dynamics of the mouse acetylcholinesterase Cys69-Cys96 omega loop
J. Biol. Chem.
278
30905-30911
2003
Mus musculus (P21836), Mus musculus
Kardos, S.A.; Sultatos, L.G.
Interactions of the organophosphates paraoxon and methyl paraoxon with mouse brain acetylcholinesterase
Toxicol. Sci.
58
118-126
2000
Mus musculus
Kovarik, Z.; Ciban, N.; Radic, Z.; Simeon-Rudolf, V.; Taylor, P.
Active site mutant acetylcholinesterase interactions with 2-PAM, HI-6, and DDVP
Biochem. Biophys. Res. Commun.
342
973-978
2006
Mus musculus
Ekstrom, F.; Akfur, C.; Tunemalm, A.K.; Lundberg, S.
Structural changes of phenylalanine 338 and histidine 447 revealed by the crystal structures of tabun-inhibited murine acetylcholinesterase
Biochemistry
45
74-81
2006
Mus musculus (P21836), Mus musculus
Kim, H.K.; Kim, M.; Kim, S.; Kim, M; Chung, J.H.
Effects of green tea polyphenol on cognitive and acetylcholinesterase activities
Biosci. Biotechnol. Biochem.
68
1977-1979
2004
Mus musculus
Cometa, M.F.; Lorenzini, P.; Fortuna, S.; Volpe, M.T.; Meneguz, A.; Palmery, M.
In vitro inhibitory effect of aflatoxin B1 on acetylcholinesterase activity in mouse brain
Toxicology
206
125-135
2005
Mus musculus
Hoernberg, A.; Tunemalm, A.K.; Ekstroem, F.
Crystal structures of acetylcholinesterase in complex with organophosphorus compounds suggest that the acyl pocket modulates the aging reaction by precluding the formation of the trigonal bipyramidal transition state
Biochemistry
46
4815-4825
2007
Mus musculus (P21836), Mus musculus
Bourne, Y.; Radic, Z.; Sulzenbacher, G.; Kim, E.; Taylor, P.; Marchot, P.
Substrate and product trafficking through the active center gorge of acetylcholinesterase analyzed by crystallography and equilibrium binding
J. Biol. Chem.
281
29256-29267
2006
Mus musculus (P21836), Mus musculus
Ko, S.O.; Kim, T.H.; Lee, H.K.; Lee, J.C.; Cho, E.S.
Temporospatial localization of acetylcholinesterase activity in the dental epithelium during mouse tooth development
Life Sci.
81
1235-1240
2007
Mus musculus
Taylor, P.; Kovarik, Z.; Reiner, E.; Radic, Z.
Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposure
Toxicology
233
70-78
2007
Mus musculus
Bosak, A.; Gazic, I.; Vinkovic, V.; Kovarik, Z.
Amino acid residues involved in stereoselective inhibition of cholinesterases with bambuterol
Arch. Biochem. Biophys.
471
72-76
2008
Mus musculus (P21836), Mus musculus
Agrawal, R.; Tyagi, E.; Shukla, R.; Nath, C.
Effect of insulin and melatonin on acetylcholinesterase activity in the brain of amnesic mice
Behav. Brain Res.
189
381-386
2008
Mus musculus
Papandreou, M.A.; Dimakopoulou, A.; Linardaki, Z.I.; Cordopatis, P.; Klimis-Zacas, D.; Margarity, M.; Lamari, F.N.
Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity
Behav. Brain Res.
198
352-358
2009
Mus musculus
Pavlov, V.A.; Parrish, W.R.; Rosas-Ballina, M.; Ochani, M.; Puerta, M.; Ochani, K.; Chavan, S.; Al-Abed, Y.; Tracey, K.J.
Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway
Brain Behav. Immun.
23
41-45
2009
Mus musculus
Vignaud, A.; Fougerousse, F.; Mouisel, E.; Guerchet, N.; Hourde, C.; Bacou, F.; Butler-Browne, G.S.; Chatonnet, A.; Ferry, A.
Genetic inactivation of acetylcholinesterase causes functional and structural impairment of mouse soleus muscles
Cell Tissue Res.
333
289-296
2008
Mus musculus
Cheng, Y.H.; Cheng, X.L.; Radi?, Z.; McCammon, J.A.
Acetylcholinesterase: mechanisms of covalent inhibition of H447I mutant determined by computational analyses
Chem. Biol. Interact.
175
196-199
2008
Mus musculus (P21836), Mus musculus
Jazi, R.; Lalonde, R.; Qian, S.; Strazielle, C.
Regional brain evaluation of acetylcholinesterase activity in PS1/A246E transgenic mice
Neurosci. Res.
63
106-114
2009
Mus musculus
Hoernberg, A.; Artursson, E.; Waerme, R.; Pang, Y.P.; Ekstroem, F.
Crystal structures of oxime-bound fenamiphos-acetylcholinesterases: reactivation involving flipping of the His447 ring to form a reactive Glu334-His447-oxime triad
Biochem. Pharmacol.
79
507-515
2010
Mus musculus (P21836), Mus musculus
Guo, L.; Suarez, A.I.; Braden, M.R.; Gerdes, J.M.; Thompson, C.M.
Inhibition of acetylcholinesterase by chromophore-linked fluorophosphonates
Bioorg. Med. Chem. Lett.
20
1194-1197
2010
Electrophorus electricus, Mus musculus
Bhattacharjee, A.K.; Kuca, K.; Musilek, K.; Gordon, R.K.
In silico pharmacophore model for tabun-inhibited acetylcholinesterase reactivators: a study of their stereoelectronic properties
Chem. Res. Toxicol.
23
26-36
2010
Mus musculus
Kakinuma, Y.; Furihata, M.; Akiyama, T.; Arikawa, M.; Handa, T.; Katare, R.G.; Sato, T.
Donepezil, an acetylcholinesterase inhibitor against Alzheimers dementia, promotes angiogenesis in an ischemic hindlimb model
J. Mol. Cell. Cardiol.
48
680-693
2010
Homo sapiens, Mus musculus
Lee, Y.K.; Yuk, D.Y.; Kim, T.I.; Kim, Y.H.; Kim, K.T.; Kim, K.H.; Lee, B.J.; Nam, S.Y.; Hong, J.T.
Protective effect of the ethanol extract of Magnolia officinalis and 4-O-methylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity
J. Nat. Med.
63
274-282
2009
Mus musculus
Artursson, E.; Andersson, P.O.; Akfur, C.; Linusson, A.; Boerjegren, S.; Ekstroem, F.
Catalytic-site conformational equilibrium in nerve-agent adducts of acetylcholinesterase: possible implications for the HI-6 antidote substrate specificity
Biochem. Pharmacol.
85
1389-1397
2013
Homo sapiens, Mus musculus (P21836), Mus musculus
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