ArticleThe EMBO journal1992
Substrate inhibition of acetylcholinesterase: residues affecting signal transduction from the surface to the catalytic center.
Article in The EMBO journal, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 227 citations in OpenAlex.
- 1-Azinyl-1'-Alkenylferrocenes with Anticholinesterase, Antioxidant, and Antiaggregating Activities as Multifunctional Agents for Potential Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Selectivity of Butyrylcholinesterase Inhibitors Revisited.Molecules (Basel, Switzerland) · 2025Review
- Expression, Characterization and Selective Chemical Inhibition of EssentialInternational journal of molecular sciences · 2025Article
- Structural insights into the putative bacterial acetylcholinesterase ChoE and its substrate inhibition mechanism.The Journal of biological chemistry · 2020Article
- The structural and biochemical impacts of monomerizing human acetylcholinesterase.Protein science : a publication of the Protein Society · 2019Article
- Kinetic Analyses of the Substrate Inhibition of Paramecium Arginine Kinase.The protein journal · 2018Article
- Characterization of butyrylcholinesterase from porcine milk.Archives of biochemistry and biophysics · 2018Article
- Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.Scientific reports · 2017Article
- Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs.Molecules (Basel, Switzerland) · 2017Review
- Functional characterisation of Schistosoma japonicum acetylcholinesterase.Parasites & vectors · 2016Article
- In vitro neuroprotective activities of compounds from Angelica shikokiana Makino.Molecules (Basel, Switzerland) · 2015Article
- Mechanism behind Resistance against the Organophosphate Azamethiphos in Salmon Lice (Lepeophtheirus salmonis).PloS one · 2015Article
- Insights and ideas garnered from marine metabolites for development of dual-function acetylcholinesterase and amyloid-β aggregation inhibitors.Marine drugs · 2014Article
- Biochemical characterization of chitin synthase activity and inhibition in the African malaria mosquito, Anopheles gambiae.Insect science · 2013Article
- Back-scattering interferometry: an ultrasensitive method for the unperturbed detection of acetylcholinesterase-inhibitor interactions.Angewandte Chemie (International ed. in English) · 2012Article
- Reaction pathway and free energy profiles for butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine.Biochemistry · 2012Article
- A tetrameric acetylcholinesterase from the parasitic nematode Dictyocaulus viviparus associates with the vertebrate tail proteins PRiMA and ColQ.Molecular and biochemical parasitology · 2012Article
- Simulations of symptomatic treatments for Alzheimer's disease: computational analysis of pathology and mechanisms of drug action.Alzheimer's research & therapy · 2012Article
- Article
- Catalytic reaction mechanism of acetylcholinesterase determined by Born-Oppenheimer ab initio QM/MM molecular dynamics simulations.The journal of physical chemistry. B · 2010Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amino acids located within and around the 'active site gorge' of human acetylcholinesterase (AChE) were substituted. Replacement of W86 yielded inactive enzyme molecules, consistent with its proposed involvement in binding of the choline moiety in the active center. A decrease in affinity to propidium and a concomitant loss of substrate inhibition was observed in D74G, D74N, D74K and W286A mutants, supporting the idea that the site for substrate inhibition and the peripheral anionic site overlap. Mutations of amino acids neighboring the active center (E202, Y337 and F338) resulted in a decrease in the catalytic and the apparent bimolecular rate constants. A decrease in affinity to edrophonium was observed in D74, E202, Y337 and to a lesser extent in F338 and Y341 mutants. E202, Y337 and Y341 mutants were not inhibited efficiently by high substrate concentrations. We propose that binding of acetylcholine, on the surface of AChE, may trigger sequence of conformational changes extending from the peripheral anionic site through W286 to D74, at the entrance of the 'gorge', and down to the catalytic center (through Y341 to F338 and Y337). These changes, especially in Y337, could block the entrance/exit of the catalytic center and reduce the catalytic efficiency of AChE.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.