ArticleThe Journal of biological chemistry2011
Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 60 citations in OpenAlex.
- Imidazole as a Pendant Reactivation Ligand Increases Efficacy Scope for Reactivation and Resurrection of Organophosphorus-Inhibited/Aged Cholinesterases by Quinone Methide Precursors.ACS chemical neuroscience · 2026Article
- Integrating multi-structure covalent docking with machine-learning consensus scoring enhances potency ranking of human acetylcholinesterase inhibitors.Briefings in bioinformatics · 2026Article
- Click-chemistry-derived oxime library reveals efficient reactivators of nerve agent-inhibited butyrylcholinesterase suitable for pseudo-catalytic bioscavenging.Archives of toxicology · 2025Article
- Applications of Microbial Organophosphate-Degrading Enzymes to Detoxification of Organophosphorous Compounds for Medical Countermeasures against Poisoning and Environmental Remediation.International journal of molecular sciences · 2024Review
- Structural and dynamic effects of paraoxon binding to human acetylcholinesterase by X-ray crystallography and inelastic neutron scattering.Structure (London, England : 1993) · 2022Article
- Assessment of four organophosphorus pesticides as inhibitors of human acetylcholinesterase and butyrylcholinesterase.Scientific reports · 2021Article
- Room temperature crystallography of human acetylcholinesterase bound to a substrate analogue 4K-TMA: Towards a neutron structure.Current research in structural biology · 2021Article
- Counteracting poisoning with chemical warfare nerve agents.Arhiv za higijenu rada i toksikologiju · 2020Review
- Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Evaluation of high-affinity phenyltetrahydroisoquinoline aldoximes, linked through anti-triazoles, as reactivators of phosphylated cholinesterases.Toxicology letters · 2020Article
- A new crystal form of human acetylcholinesterase for exploratory room-temperature crystallography studies.Chemico-biological interactions · 2019Article
- Productive reorientation of a bound oxime reactivator revealed in room temperature X-ray structures of native and VX-inhibited human acetylcholinesterase.The Journal of biological chemistry · 2019Article
- Cholinesterase Inhibitor Therapy in Alzheimer's Disease: The Limits and Tolerability of Irreversible CNS-Selective Acetylcholinesterase Inhibition in Primates.Journal of Alzheimer's disease : JAD · 2017Article
- Organophosphate-Hydrolyzing Enzymes as First-Line of Defence Against Nerve Agent-Poisoning: Perspectives and the Road Ahead.The protein journal · 2016Review
- HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants.Chemico-biological interactions · 2016Article
- Novel Organophosphate Ligand O-(2-Fluoroethyl)-O-(p-Nitrophenyl)Methylphosphonate: Synthesis, Hydrolytic Stability and Analysis of the Inhibition and Reactivation of Cholinesterases.Chemical research in toxicology · 2016Article
- Resolving pathways of interaction of mipafox and a sarin analog with human acetylcholinesterase by kinetics, mass spectrometry and molecular modeling approaches.Archives of toxicology · 2016Article
- Catalytic Soman Scavenging by the Y337A/F338A Acetylcholinesterase Mutant Assisted with Novel Site-Directed Aldoximes.Chemical research in toxicology · 2015Article
- Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification.Journal of medicinal chemistry · 2014Article
- Centrally acting oximes in reactivation of tabun-phosphoramidated AChE.Chemico-biological interactions · 2013Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase, are primary targets of organophosphates (OPs). Exposure to OPs can lead to serious cardiovascular complications, respiratory compromise, and death. Current therapy to combat OP poisoning involves an oxime reactivator (2-PAM, obidoxime, TMB4, or HI-6) combined with atropine and on occasion an anticonvulsant. Butyrylcholinesterase, administered in the plasma compartment as a bio-scavenger, has also shown efficacy but is limited by its strict stoichiometric scavenging, slow reactivation, and a propensity for aging. Here, we characterize 10 human (h) AChE mutants that, when coupled with an oxime, give rise to catalytic reactivation and aging resistance of the soman conjugate. With the most efficient human AChE mutant Y337A/F338A, we show enhanced reactivation rates for several OP-hAChE conjugates compared with wild-type hAChE when reactivated with HI-6 (1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4'-carbamoyl-1-pyridinium)). In addition, we interrogated an 840-member novel oxime library for reactivation of Y337A/F338A hAChE-OP conjugates to delineate the most efficient oxime-mutant enzyme pairs for catalytic bio-scavenging. Combining the increased accessibility of the Y337A mutation to oximes within the space-impacted active center gorge with the aging resistance of the F338A mutation provides increased substrate diversity in scavenging potential for aging-prone alkyl phosphate inhibitors.
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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.