Structural fractal analysis of the active sites of acetylcholinesterase from various organisms

Veniamin Grigorev; Oleg Tinkov; Ludmila Grigoreva; Alexander Rasdolsky

doi:10.1016/j.jmgm.2022.108265

Structural fractal analysis of the active sites of acetylcholinesterase from various organisms

J Mol Graph Model. 2022 Nov:116:108265. doi: 10.1016/j.jmgm.2022.108265. Epub 2022 Jul 5.

Authors

Veniamin Grigorev¹, Oleg Tinkov², Ludmila Grigoreva³, Alexander Rasdolsky⁴

Affiliations

¹ Department of Computer-aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy proezd 1, 142432, Chernogolovka, Moscow region, Russia. Electronic address: beng@ipac.ac.ru.
² Department of Pharmacology and Pharmaceutical Chemistry, Medical Faculty, Transnistrian State University, October 25 Str. 128, 3300, Tiraspol, Transdniestria, Republic of Moldova.
³ Department of Fundamental Physical and Chemical Engineering, Moscow State University, Leninskiye Gory 1/51, 119991, Moscow, Russia.
⁴ Department of Computer-aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severniy proezd 1, 142432, Chernogolovka, Moscow region, Russia.

PMID: 35816907
DOI: 10.1016/j.jmgm.2022.108265

Abstract

Acetylcholinesterase (AChE) is the object of many studies due to the fact that it plays an important role in the vital activity of organisms. In particular, when new AChE inhibitors are developed, much attention is paid to the specificity of their action. One of the approaches used to study the specificity is to compare AChE taken from various organisms. In this work, crystallographic data are used to investigate the active sites of AChE (ASAs) in the free (uncomplexed) state for the following five organisms: Homo sapiens (HS), Mus musculus (MM), Torpedo californica (TC), Electrophorus electricus (EE), and Drosophila melanogaster (DM). The structural fractal analysis (SFA) proposed by us earlier is used as a research method. This method is based on the calculation and comparison of the fractal dimensions of molecular structures. SFA demonstrates that there are no significant structural differences between the active sites of human AChE and other AChEs. However, differences are found for the MM/EE pair. Further analysis of individual AARs has revealed two different areas of active sites. Ser203, Trp236, Phe338, and Tyr341 are found to belong to a variable region, and the remaining AARs belong to a conservative region of the ASAs. The fraction of "variability" is low, 0.8%.

Keywords: Acetylcholinesterase; Active sites; Fractal dimension; Histogram; Variability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase* / chemistry
Animals
Catalytic Domain
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology
Drosophila melanogaster
Electrophorus / metabolism
Fractals*
Humans
Mice
Torpedo / metabolism

Substances

Cholinesterase Inhibitors
Acetylcholinesterase