ArticleBiophysical journal2010
Long route or shortcut? A molecular dynamics study of traffic of thiocholine within the active-site gorge of acetylcholinesterase.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Acetylcholinesterase: Structure, dynamics, and interactions with organophosphorus compounds.Protein science : a publication of the Protein Society · 2025Review
- Article
- CNEURO-201, an Anti-amyloidogenic Agent and σ1-Receptor Agonist, Improves Cognition in theInternational journal of molecular sciences · 2025Article
- Enzyme Dynamics Determine the Potency and Selectivity of Inhibitors Targeting Disease-Transmitting Mosquitoes.ACS infectious diseases · 2024Article
- Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower ofMolecules (Basel, Switzerland) · 2022Article
- Molecular Recognition of Nerve Agents and Their Organophosphorus Surrogates: Toward Supramolecular Scavengers and Catalysts.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Review
- A Comprehensive Review of Cholinesterase Modeling and Simulation.Biomolecules · 2021Review
- Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Review
- Hot Spots for Protein Partnerships at the Surface of Cholinesterases and Related α/β Hydrolase Fold Proteins or Domains-A Structural Perspective.Molecules (Basel, Switzerland) · 2017Review
- Computational Studies on Acetylcholinesterases.Molecules (Basel, Switzerland) · 2017Review
- Gorge Motions of Acetylcholinesterase Revealed by Microsecond Molecular Dynamics Simulations.Scientific reports · 2017Article
- Crystal structure of snake venom acetylcholinesterase in complex with inhibitory antibody fragment Fab410 bound at the peripheral site: evidence for open and closed states of a back door channel.The Journal of biological chemistry · 2015Article
- A wrench in the works of human acetylcholinesterase: soman induced conformational changes revealed by molecular dynamics simulations.PloS one · 2015Article
- Free energy landscape for the binding process of Huperzine A to acetylcholinesterase.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- Structural and functional characterization of the interaction of the photosensitizing probe methylene blue with Torpedo californica acetylcholinesterase.Protein science : a publication of the Protein Society · 2012Article
- Kinetics of Torpedo californica acetylcholinesterase inhibition by bisnorcymserine and crystal structure of the complex with its leaving group.The Biochemical journal · 2012Article
- Backdoor opening mechanism in acetylcholinesterase based on X-ray crystallography and molecular dynamics simulations.Protein science : a publication of the Protein Society · 2011Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The principal role of acetylcholinesterase is termination of nerve impulse transmission at cholinergic synapses, by rapid hydrolysis of the neurotransmitter acetylcholine to acetate and choline. Its active site is buried at the bottom of a deep and narrow gorge, at the rim of which is found a second anionic site, the peripheral anionic site. The fact that the active site is so deeply buried has raised cogent questions as to how rapid traffic of substrate and products occurs in such a confined environment. Various theoretical and experimental approaches have been used to solve this problem. Here, multiple conventional molecular dynamics simulations have been performed to investigate the clearance of the product, thiocholine, from the active-site gorge of acetylcholinesterase. Our results indicate that thiocholine is released from the peripheral anionic site via random pathways, while three exit routes appear to be favored for its release from the active site, namely, along the axis of the active-site gorge, and through putative back- and side-doors. The back-door pathway is that via which thiocholine exits most frequently. Our results are in good agreement with kinetic and kinetic-crystallography studies. We propose the use of multiple molecular dynamics simulations as a fast yet accurate complementary tool in structural studies of enzymatic trafficking.
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