ArticleProceedings of the National Academy of Sciences of the United States of America2018
Cryo-EM structure of the native butyrylcholinesterase tetramer reveals a dimer of dimers stabilized by a superhelical assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Phytochemistry, bioactivity, andRSC advances · 2026Article
- Expanding cholinesterase function: kinetic and structural evidence for hydrolysis of long-chain fatty-acid esters.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Expression, purification, and in vitro characterization of the carboxylesterase CEST-9.2 from Caenorhabditis elegans.Bioscience reports · 2026Article
- New views on physiological functions and regulation of butyrylcholinesterase and potential therapeutic interventions.Frontiers in molecular biosciences · 2025Review
- Association of Butyryl Cholinesterase and Recurrent Ischemic Stroke: A Cross-Sectional Study.International journal of general medicine · 2025Article
- Activation/Inhibition of Cholinesterases by Excess Substrate: Interpretation of the PhenomenologicalInternational journal of molecular sciences · 2023Article
- Human butyrylcholinesterase in Cohn fraction IV-4 purified in a single chromatography step on Hupresin.PloS one · 2023Article
- Conformational Stability and Denaturation Processes of Proteins Investigated by Electrophoresis under Extreme Conditions.Molecules (Basel, Switzerland) · 2022Review
- Butyrylcholinesterase in SH-SY5Y human neuroblastoma cells.Neurotoxicology · 2022Article
- Butyrylcholinesterase-Protein Interactions in Human Serum.International journal of molecular sciences · 2021Article
- Cryo-electron microscopy of cholinesterases, present and future.Journal of neurochemistry · 2021Review
- A Comprehensive Review of Cholinesterase Modeling and Simulation.Biomolecules · 2021Review
- Characterization of four BCHE mutations associated with prolonged effect of suxamethonium.The pharmacogenomics journal · 2021Article
- Cholinesterases in Tripartite Neuromuscular Synapse.Frontiers in molecular neuroscience · 2021Review
- Polyproline-rich peptides associated with Torpedo californica acetylcholinesterase tetramers.Chemico-biological interactions · 2020Article
- Chlorpyrifos Oxon-Induced Isopeptide Bond Formation in Human Butyrylcholinesterase.Molecules (Basel, Switzerland) · 2020Article
- Purification of human butyrylcholinesterase from frozen Cohn fraction IV-4 by ion exchange and Hupresin affinity chromatography.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
The quaternary structures of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are essential for their localization and function. Of practical importance, BChE is a promising therapeutic candidate for intoxication by organophosphate nerve agents and insecticides, and for detoxification of addictive substances. Efficacy of the recombinant enzyme hinges on its having a long circulatory half-life; this, in turn, depends strongly on its ability to tetramerize. Here, we used cryoelectron microscopy (cryo-EM) to determine the structure of the highly glycosylated native BChE tetramer purified from human plasma at 5.7 Å. Our structure reveals that the BChE tetramer is organized as a staggered dimer of dimers. Tetramerization is mediated by assembly of the C-terminal tryptophan amphiphilic tetramerization (WAT) helices from each subunit as a superhelical assembly around a central lamellipodin-derived oligopeptide with a proline-rich attachment domain (PRAD) sequence that adopts a polyproline II helical conformation and runs antiparallel. The catalytic domains within a dimer are asymmetrically linked to the WAT/PRAD. In the resulting arrangement, the tetramerization domain is largely shielded by the catalytic domains, which may contribute to the stability of the human BChE (HuBChE) tetramer. Our cryo-EM structure reveals the basis for assembly of the native tetramers and has implications for the therapeutic applications of HuBChE. This mode of tetramerization is seen only in the cholinesterases but may provide a promising template for designing other proteins with improved circulatory residence times.
Indexed as
Identifiers
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.