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The role of electrostatic interactions in the absorption of ligands to the active sites of cholinesterases, as indicated by molecular modeling data

Abstract

The effect of electrostatic interactions on the absorption of the positively charged reversible inhibitor tetram-ethylammonium, its neutral structural analogue neopentane C(CH3)4, and the natural substrate acethylcholine to the active sites of acetylcholinesterase and butyrylcholinesterase has been studied by molecular modeling methods. It has been shown that the dominant absorption of positively charged ligands is due to the anchoring of the cationic group of the ligand in the anionic subsite of both enzymes through the interaction of the π-cation with the benzene ring of tryptophan. The correlation between the free energy of complex formation and the catalytic activity of charged tetramethylammonium has been revealed for both enzymes. It has been shown that the effective binding of the acetylcholine molecule requires the additional activation of the enzyme.

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Abbreviations

AChE:

acetylcholinesterase

BChE:

butyrylcholinesterase

Ach:

acetylcholine

PAS:

peripheral anionic site

TMA:

tetramethylammonium

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Correspondence to D. A. Belinskaya.

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Original Russian Text © D.A. Belinskaya, A.H. Juffer, N.N. Shestakova, 2010, published in Bioorganicheskaya Khimiya, 2010, Vol. 36, No. 2, pp. 200–205.

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Belinskaya, D.A., Juffer, A.H. & Shestakova, N.N. The role of electrostatic interactions in the absorption of ligands to the active sites of cholinesterases, as indicated by molecular modeling data. Russ J Bioorg Chem 36, 185–190 (2010). https://doi.org/10.1134/S106816201002007X

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  • DOI: https://doi.org/10.1134/S106816201002007X

Key words

  • acetylcholinesterase
  • butyrylcholinesterase
  • tetramethylammonium
  • neopentane
  • acetylcholine
  • molecular modeling