ArticleBiochemistry2012
Reaction pathway and free energy profiles for butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Computer-aided Drug Design for Alzheimer's Disease: Recent Advancements and Future Perspectives.Current topics in medicinal chemistry · 2026Review
- 1-Azinyl-1'-Alkenylferrocenes with Anticholinesterase, Antioxidant, and Antiaggregating Activities as Multifunctional Agents for Potential Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Article
- An Integrated Nanosensor/Smartphone Platform for Point-of-Care Biomonitoring of Human Exposure to Pesticides.Analytical chemistry · 2025Article
- Article
- A Comprehensive Review of Cholinesterase Modeling and Simulation.Biomolecules · 2021Review
- Catalytic Reaction Mechanism for Drug Metabolism in Human Carboxylesterase-1: Cocaine Hydrolysis Pathway.Molecular pharmaceutics · 2018Article
- Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity.Scientific reports · 2017Article
- Catalytic Mechanisms for Cofactor-Free Oxidase-Catalyzed Reactions: Reaction Pathways of Uricase-Catalyzed Oxidation and Hydration of Uric Acid.ACS catalysis · 2017Article
- Ensemble Molecular Dynamics of a Protein-Ligand Complex: Residual Inhibitor Entropy Enhances Drug Potency in Butyrylcholinesterase.Bioenergetics : open access · 2017Article
- Quantum mechanics implementation in drug-design workflows: does it really help?Drug design, development and therapy · 2017Review
- Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of "hunger hormone" ghrelin.Scientific reports · 2016Article
- Reaction Pathway for Cocaine Hydrolase-Catalyzed Hydrolysis of (+)-Cocaine.Theoretical chemistry accounts · 2016Article
- Fundamental reaction pathway and free energy profile of proteasome inhibition by syringolin A (SylA).Organic & biomolecular chemistry · 2015Article
- Reaction pathways and free energy profiles for cholinesterase-catalyzed hydrolysis of 6-monoacetylmorphine.Organic & biomolecular chemistry · 2014Article
- Substrate selectivity of high-activity mutants of human butyrylcholinesterase.Organic & biomolecular chemistry · 2013Article
- Fundamental reaction pathway for peptide metabolism by proteasome: insights from first-principles quantum mechanical/molecular mechanical free energy calculations.The journal of physical chemistry. B · 2013Article
- Fundamental reaction pathway and free energy profile for butyrylcholinesterase-catalyzed hydrolysis of heroin.Biochemistry · 2013Article
- Reaction pathway and free energy profile for papain-catalyzed hydrolysis of N-acetyl-Phe-Gly 4-nitroanilide.Biochemistry · 2013Article
- Catalytic mechanism of cytochrome P450 for N-methylhydroxylation of nicotine: reaction pathways and regioselectivity of the enzymatic nicotine oxidation.Dalton transactions (Cambridge, England : 2003) · 2013Article
- Fundamental reaction pathway and free energy profile for inhibition of proteasome by Epoxomicin.Journal of the American Chemical Society · 2012Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
The catalytic mechanism for butyrylcholineserase (BChE)-catalyzed hydrolysis of acetylthiocholine (ATCh) has been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical-free energy (QM/MM-FE) calculations on both acylation and deacylation of BChE. Additional quantum mechanical (QM) calculations have been carried out, along with the QM/MM-FE calculations, to understand the known substrate activation effect on the enzymatic hydrolysis of ATCh. It has been shown that the acylation of BChE with ATCh consists of two reaction steps including the nucleophilic attack on the carbonyl carbon of ATCh and the dissociation of thiocholine ester. The deacylation stage includes nucleophilic attack of a water molecule on the carboxyl carbon of substrate and dissociation between the carboxyl carbon of substrate and hydroxyl oxygen of Ser198 side chain. QM/MM-FE calculation results reveal that the acylation of BChE is rate-determining. It has also been demonstrated that an additional substrate molecule binding to the peripheral anionic site (PAS) of BChE is responsible for the substrate activation effect. In the presence of this additional substrate molecule at PAS, the calculated free energy barrier for the acylation stage (rate-determining step) is decreased by ~1.7 kcal/mol. All of our computational predictions are consistent with available experimental kinetic data. The overall free energy barriers calculated for BChE-catalyzed hydrolysis of ATCh at regular hydrolysis phase and substrate activation phase are ~13.6 and ~11.9 kcal/mol, respectively, which are in reasonable agreement with the corresponding experimentally derived activation free energies of 14.0 kcal/mol (for regular hydrolysis phase) and 13.5 kcal/mol (for substrate activation phase).
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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.