Top ▲
Target id: 2465
Nomenclature: acetylcholinesterase (Yt blood group)
Abbreviated Name: AChE
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 614 | 7q22.1 | ACHE | acetylcholinesterase (Yt blood group) | |
Mouse | - | 614 | 5 76.32 cM | Ache | acetylcholinesterase | |
Rat | - | 614 | 12q12 | Ache | acetylcholinesterase |
Previous and Unofficial Names |
acetylcholinesterase | acetylcholinesterase (Cartwright blood group) |
Database Links | |
Alphafold | P22303 (Hs), P21836 (Mm), P37136 (Rn) |
BRENDA | 3.1.1.7 |
CATH/Gene3D | 3.40.50.1820 |
ChEMBL Target | CHEMBL220 (Hs), CHEMBL3198 (Mm), CHEMBL3199 (Rn) |
DrugBank Target | P22303 (Hs) |
Ensembl Gene | ENSG00000087085 (Hs), ENSMUSG00000023328 (Mm), ENSRNOG00000050841 (Rn) |
Entrez Gene | 43 (Hs), 11423 (Mm) |
Human Protein Atlas | ENSG00000087085 (Hs) |
KEGG Enzyme | 3.1.1.7 |
KEGG Gene | hsa:43 (Hs), mmu:11423 (Mm) |
OMIM | 100740 (Hs) |
Pharos | P22303 (Hs) |
RefSeq Nucleotide | NM_015831 (Hs), NM_009599 (Mm), NM_172009 (Rn) |
RefSeq Protein | NP_056646 (Hs), NP_033729 (Mm), NP_742006 (Rn) |
SynPHARM |
78555 (in complex with donepezil) 78675 (in complex with galantamine) |
UniProtKB | P22303 (Hs), P21836 (Mm), P37136 (Rn) |
Wikipedia | ACHE (Hs) |
Selected 3D Structures | |||||||||||||
|
Enzyme Reaction | ||||
|
Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||
|
Immuno Process Associations | ||
|
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. |
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 USA, 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]