Top ▲

acetylcholinesterase (Cartwright blood group)

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2465

Nomenclature: acetylcholinesterase (Cartwright blood group)

Abbreviated Name: AChE

Family: Acetylcholine turnover, Hydrolases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 614 7q22 ACHE acetylcholinesterase (Cartwright blood group)
Mouse - 614 5 G2 Ache acetylcholinesterase
Rat - 614 12 Ache acetylcholinesterase
Previous and Unofficial Names Click here for help
Yt blood group | acetylcholinesterase | acetylcholinesterase (Yt blood group)
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Donepezil
PDB Id:  4EY7
Ligand:  donepezil
Resolution:  2.35Å
Species:  Human
References:  4
Enzyme Reaction Click here for help
EC Number: 3.1.1.7 Acetylcholine + H2O = acetic acid + choline + H+

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
tacrine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pKi 2
pKi 7.5 (Ki 3x10-8 M) [2]
edrophonium Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 6.7 pKi 1
pKi 6.7 (Ki 2x10-7 M) [1]
Description: Using the chloride salt
compound 2f [Jiang et al., 2018] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.2 pIC50 8
pIC50 8.2 (IC50 6.5x10-9 M) [8]
donepezil Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.7 – 8.3 pIC50 3,6,11
pIC50 7.7 – 8.3 [3,6,11]
donecopride Small molecule or natural product Hs Inhibition 7.8 pIC50 10
pIC50 7.8 (IC50 1.6x10-8 M) [10]
physostigmine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 – 7.8 pIC50 11
pIC50 7.6 – 7.8 [11]
BW284C51 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.7 pIC50 7
pIC50 7.7 [7]
neostigmine Small molecule or natural product Approved drug Hs Inhibition 7.3 pIC50 9
pIC50 7.3 (IC50 4.5x10-8 M) [9]
Description: Inhibition of ACHE activity in human serum.
pyridostigmine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.4 pIC50 14
pIC50 6.4 (IC50 3.6x10-7 M) [14]
Description: Inhibition of human erythrocyte ACHE activity by a modified Ellman assay.
galantamine Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 6.3 pIC50 5
pIC50 6.3 (IC50 5x10-7 M) [5]
rivastigmine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.4 pIC50 11
pIC50 5.4 (IC50 4.15x10-6 M) [11]
pralidoxime Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 3.1 pIC50 12
pIC50 3.1 (IC50 8.78x10-4 M) [12]
Description: Inhibition of human recombinant AChE by modified Ellman's method.
echothiophate Small molecule or natural product Approved drug Hs Inhibition - -
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AChE reactivator 2 Small molecule or natural product Hs - 5.6 pIC50 13
pIC50 5.6 (IC50 2.3x10-6 M) [13]
Description: Measuring reactivation of hAChE.
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0031623 receptor internalization IEA
General Comments
Acetylcholinesterase (AChE) is found at cholinergic synapses throughout the nervous system and at neuromuscular junctions where it rapidly hydrolyses the neurotransmitter acetylcholine (ACh) and in so doing terminates synaptic transmission. AChE is the primary target of organophosphorus (OP) pesticides and nerve agents. PO agents inhibit enzymatic activity by attaching a phosphyl group at AChE's active-site serine. OP nerve agent antidotes work by displacing the blocking phosphyl group and thus reactivate the enzyme.
It has been shown that ACHE corresponds to the Yt blood group antigen. For more details see the OMIM entry 112100.

References

Show »

1. Boyle NA, Talesa V, Giovannini E, Rosi G, Norton SJ. (1997) Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase. J. Med. Chem., 40 (19): 3009-13. [PMID:9301662]

2. Butini S, Campiani G, Borriello M, Gemma S, Panico A, Persico M, Catalanotti B, Ros S, Brindisi M, Agnusdei M et al.. (2008) Exploiting protein fluctuations at the active-site gorge of human cholinesterases: further optimization of the design strategy to develop extremely potent inhibitors. J. Med. Chem., 51 (11): 3154-70. [PMID:18479118]

3. Cardozo MG, Iimura Y, Sugimoto H, Yamanishi Y, Hopfinger AJ. (1992) QSAR analyses of the substituted indanone and benzylpiperidine rings of a series of indanone-benzylpiperidine inhibitors of acetylcholinesterase. J. Med. Chem., 35 (3): 584-9. [PMID:1738151]

4. Cheung J, Rudolph MJ, Burshteyn F, Cassidy MS, Gary EN, Love J, Franklin MC, Height JJ. (2012) Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J. Med. Chem., 55 (22): 10282-6. [PMID:23035744]

5. Clark JK, Cowley P, Muir AW, Palin R, Pow E, Prosser AB, Taylor R, Zhang MQ. (2002) Quaternary salts of E2020 analogues as acetylcholinesterase inhibitors for the reversal of neuromuscular block. Bioorg. Med. Chem. Lett., 12 (18): 2565-8. [PMID:12182861]

6. Galli A, Mori F, Benini L, Cacciarelli N. (1994) Acetylcholinesterase protection and the anti-diisopropylfluorophosphate efficacy of E2020. Eur. J. Pharmacol., 270 (2-3): 189-93. [PMID:8039548]

7. Giacobini E. (2003) Cholinesterases: new roles in brain function and in Alzheimer's disease. Neurochem. Res., 28 (3-4): 515-22. [PMID:12675140]

8. Jiang XY, Chen TK, Zhou JT, He SY, Yang HY, Chen Y, Qu W, Feng F, Sun HP. (2018) Dual GSK-3β/AChE Inhibitors as a New Strategy for Multitargeting Anti-Alzheimer's Disease Drug Discovery. ACS Med Chem Lett, 9 (3): 171-176. [PMID:29541355]

9. Kavitha CV, Gaonkar SL, Narendra Sharath Chandra JN, Sadashiva CT, Rangappa KS. (2007) Synthesis and screening for acetylcholinesterase inhibitor activity of some novel 2-butyl-1,3-diaza-spiro[4,4]non-1-en-4-ones: derivatives of irbesartan key intermediate. Bioorg. Med. Chem., 15 (23): 7391-8. [PMID:17888667]

10. Lecoutey C, Hedou D, Freret T, Giannoni P, Gaven F, Since M, Bouet V, Ballandonne C, Corvaisier S, Malzert Fréon A et al.. (2014) Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment. Proc. Natl. Acad. Sci. U.S.A., 111 (36): E3825-30. [PMID:25157130]

11. Luo W, Yu QS, Kulkarni SS, Parrish DA, Holloway HW, Tweedie D, Shafferman A, Lahiri DK, Brossi A, Greig NH. (2006) Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine. J. Med. Chem., 49 (7): 2174-85. [PMID:16570913]

12. Musilek K, Komloova M, Holas O, Horova A, Pohanka M, Gunn-Moore F, Dohnal V, Dolezal M, Kuca K. (2011) Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage-Preparation, in vitro screening and molecular docking. Bioorg. Med. Chem., 19 (2): 754-62. [PMID:21215642]

13. Santoni G, de Sousa J, de la Mora E, Dias J, Jean L, Sussman JL, Silman I, Renard PY, Brown RCD, Weik M et al.. (2018) Structure-Based Optimization of Nonquaternary Reactivators of Acetylcholinesterase Inhibited by Organophosphorus Nerve Agents. J. Med. Chem., 61 (17): 7630-7639. [PMID:30125110]

14. Yu QS, Holloway HW, Luo W, Lahiri DK, Brossi A, Greig NH. (2010) Long-acting anticholinesterases for myasthenia gravis: synthesis and activities of quaternary phenylcarbamates of neostigmine, pyridostigmine and physostigmine. Bioorg. Med. Chem., 18 (13): 4687-93. [PMID:20627738]

How to cite this page