ArticleThe EMBO journal1994
Electrostatic attraction by surface charge does not contribute to the catalytic efficiency of acetylcholinesterase.
Article in The EMBO journal, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Purification of Human Immunoglobulin G with Bathophenanthroline-ZnAntibodies (Basel, Switzerland) · 2025Article
- Acetylcholinesterase: A Versatile Template to Coin Potent Modulators of Multiple Therapeutic Targets.Accounts of chemical research · 2024Article
- Computational Studies on Acetylcholinesterases.Molecules (Basel, Switzerland) · 2017Review
- A wrench in the works of human acetylcholinesterase: soman induced conformational changes revealed by molecular dynamics simulations.PloS one · 2015Article
- Interaction of acetylcholinesterase with neurexin-1β regulates glutamatergic synaptic stability in hippocampal neurons.Molecular brain · 2014Article
- Long route or shortcut? A molecular dynamics study of traffic of thiocholine within the active-site gorge of acetylcholinesterase.Biophysical journal · 2010Article
- Acetylcholinesterase: from 3D structure to function.Chemico-biological interactions · 2010Article
- Influence of the water structure on the acetylcholinesterase efficiency.Biophysical journal · 2005Article
- Excessive expression of acetylcholinesterase impairs glutamatergic synaptogenesis in hippocampal neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2004Article
- Acetylcholinesterase: a multifaceted target for structure-based drug design of anticholinesterase agents for the treatment of Alzheimer's disease.Journal of molecular neuroscience : MN · 2003Review
- Overloading and removal of N-glycosylation targets on human acetylcholinesterase: effects on glycan composition and circulatory residence time.The Biochemical journal · 2002Article
- A modular treatment of molecular traffic through the active site of cholinesterase.Biophysical journal · 1999Article
- Bovine acetylcholinesterase: cloning, expression and characterization.The Biochemical journal · 1998Article
- Electrostatic steering and ionic tethering in enzyme-ligand binding: insights from simulations.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Backbone makes a significant contribution to the electrostatics of alpha/beta-barrel proteins.Protein science : a publication of the Protein Society · 1997Article
- Electrooptical measurements demonstrate a large permanent dipole moment associated with acetylcholinesterase.Biophysical journal · 1996Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetylcholinesterases (AChEs) are characterized by a high net negative charge and by an uneven surface charge distribution, giving rise to a negative electrostatic potential extending over most of the molecular surface. To evaluate the contribution of these electrostatic properties to the catalytic efficiency, 20 single- and multiple-site mutants of human AChE were generated by replacing up to seven acidic residues, vicinal to the rim of the active-center gorge (Glu84, Glu285, Glu292, Asp349, Glu358, Glu389 and Asp390), by neutral amino acids. Progressive simulated replacement of these charged residues results in a gradual decrease of the negative electrostatic potential which is essentially eliminated by neutralizing six or seven charges. In marked contrast to the shrinking of the electrostatic potential, the corresponding mutations had no significant effect on the apparent bimolecular rate constants of hydrolysis for charged and non-charged substrates, or on the Ki value for a charged active center inhibitor. Moreover, the kcat values for all 20 mutants are essentially identical to that of the wild type enzyme, and the apparent bimolecular rate constants show a moderate dependence on the ionic strength, which is invariant for all the enzymes examined. These findings suggest that the surface electrostatic properties of AChE do not contribute to the catalytic rate, that this rate is probably not diffusion-controlled and that long-range electrostatic interactions play no role in stabilization of the transition states of the catalytic process.
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