ArticleThe EMBO journal2006
Structural insights into substrate traffic and inhibition in acetylcholinesterase.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 198 citations in OpenAlex.
- Protein structural dynamics in covalent drug design: insights from irreversible and reversible covalent inhibitors.RSC chemical biology · 2026Review
- Structural and Mechanistic Insights into Dual Cholinesterase Inhibition by Marine Phytohormones.Marine drugs · 2026Article
- Acetylcholinesterase as a Multifunctional Target in Amyloid-Driven Neurodegeneration: From Dual-Site Inhibitors to Anti-Agregation Strategies.International journal of molecular sciences · 2025Review
- In Vitro Evaluation of Novel Furo[3,2-Molecules (Basel, Switzerland) · 2025Article
- Cholinergic Inhibition and Antioxidant Potential of Gongronema latifolium Benth Leaf in Neurodegeneration: Experimental and In Silico Study.Cell biochemistry and biophysics · 2025Article
- Mechanistic and Therapeutic Insights into Flavonoid-Based Inhibition of Acetylcholinesterase: Implications for Neurodegenerative Diseases.Nutrients · 2024Review
- Antioxidant, anti-acetylcholinesterase, and anti-amyloid-β peptide aggregations of hispolon and its analogs in vitro and improved learning and memory functions in scopolamine-induced ICR mice.Botanical studies · 2024Article
- Advances in Cholinesterase Inhibitor Research-An Overview of Preclinical Studies of Selected Organoruthenium(II) Complexes.International journal of molecular sciences · 2024Review
- Uncovering the genetic diversity in Aedes aegypti insecticide resistance genes through global comparative genomics.Scientific reports · 2024Article
- Evaluation of Anticholinesterase Activity of the Fungicides Mefentrifluconazole and Pyraclostrobin.International journal of molecular sciences · 2024Article
- Identification of potential inhibitors of cholinergic and β-secretase enzymes from phytochemicals derived from Gongronema latifolium Benth leaf: an integrated computational analysis.Molecular diversity · 2024Article
- Acetylcholinesterase: A Versatile Template to Coin Potent Modulators of Multiple Therapeutic Targets.Accounts of chemical research · 2024Article
- The effects of FeBioImpacts : BI · 2024Article
- Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A.Current research in structural biology · 2024Article
- Profiling Novel Quinuclidine-Based Derivatives as Potential Anticholinesterase Drugs: Enzyme Inhibition and Effects on Cell Viability.International journal of molecular sciences · 2023Article
- 8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2023Article
- Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations.Molecules (Basel, Switzerland) · 2022Article
- Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action.Molecules (Basel, Switzerland) · 2022Article
- Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetylcholinesterase (AChE) terminates nerve-impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter, acetylcholine. Substrate traffic in AChE involves at least two binding sites, the catalytic and peripheral anionic sites, which have been suggested to be allosterically related and involved in substrate inhibition. Here, we present the crystal structures of Torpedo californica AChE complexed with the substrate acetylthiocholine, the product thiocholine and a nonhydrolysable substrate analogue. These structures provide a series of static snapshots of the substrate en route to the active site and identify, for the first time, binding of substrate and product at both the peripheral and active sites. Furthermore, they provide structural insight into substrate inhibition in AChE at two different substrate concentrations. Our structural data indicate that substrate inhibition at moderate substrate concentration is due to choline exit being hindered by a substrate molecule bound at the peripheral site. At the higher concentration, substrate inhibition arises from prevention of exit of acetate due to binding of two substrate molecules within the active-site gorge.
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