ArticleBiophysical journal2008
Dynamics of the acetylcholinesterase tetramer.
Article in Biophysical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi-enzyme colocalization and environment.Protein science : a publication of the Protein Society · 2024Article
- Phenoxyethyl Piperidine/Morpholine Derivatives as PAS and CAS Inhibitors of Cholinesterases: Insights for Future Drug Design.Scientific reports · 2019Article
- 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
- Rate Constants and Mechanisms of Protein-Ligand Binding.Annual review of biophysics · 2017Review
- Secondary Interaction Interfaces with PCNA Control Conformational Switching of DNA Polymerase PolB from Polymerization to Editing.The journal of physical chemistry. B · 2016Article
- Investigation of Structural Dynamics of Enzymes and Protonation States of Substrates Using Computational Tools.Catalysts (Basel, Switzerland) · 2016Article
- Research on the regulation of the spatial structure of acetylcholinesterase tetramer with high efficiency by AFM.International journal of nanomedicine · 2013Article
- Theory and simulation of diffusion-influenced, stochastically gated ligand binding to buried sites.The Journal of chemical physics · 2011Article
- Active site gating and substrate specificity of butyrylcholinesterase and acetylcholinesterase: insights from molecular dynamics simulations.The journal of physical chemistry. B · 2011Article
- Theory and simulation on the kinetics of protein-ligand binding coupled to conformational change.The Journal of chemical physics · 2011Article
- Gated Diffusion-controlled Reactions.BMC biophysics · 2011Article
- Evidence for impaired vagus nerve activity in heart failure.Heart failure reviews · 2011Review
- Enzymatic activity versus structural dynamics: the case of acetylcholinesterase tetramer.Biophysical journal · 2009Article
- Model of human butyrylcholinesterase tetramer by homology modeling and dynamics simulation.The journal of physical chemistry. B · 2009Article
- Multiscale methods for macromolecular simulations.Current opinion in structural biology · 2008Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Acetylcholinesterase rapidly hydrolyzes the neurotransmitter acetylcholine in cholinergic synapses, including the neuromuscular junction. The tetramer is the most important functional form of the enzyme. Two low-resolution crystal structures have been solved. One is compact with two of its four peripheral anionic sites (PAS) sterically blocked by complementary subunits. The other is a loose tetramer with all four subunits accessible to solvent. These structures lacked the C-terminal amphipathic t-peptide (WAT domain) that interacts with the proline-rich attachment domain (PRAD). A complete tetramer model (AChEt) was built based on the structure of the PRAD/WAT complex and the compact tetramer. Normal mode analysis suggested that AChEt could exist in several conformations with subunits fluctuating relative to one another. Here, a multiscale simulation involving all-atom molecular dynamics and C alpha-based coarse-grained Brownian dynamics simulations was carried out to investigate the large-scale intersubunit dynamics in AChEt. We sampled the ns-mus timescale motions and found that the tetramer indeed constitutes a dynamic assembly of monomers. The intersubunit fluctuation is correlated with the occlusion of the PAS. Such motions of the subunits "gate" ligand-protein association. The gates are open more than 80% of the time on average, which suggests a small reduction in ligand-protein binding. Despite the limitations in the starting model and approximations inherent in coarse graining, these results are consistent with experiments which suggest that binding of a substrate to the PAS is only somewhat hindered by the association of the subunits.
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What OpenQuestion holds
Registered trials
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.