Molecular Modeling Studies on the Interactions of Aflatoxin B1 and Its Metabolites with Human Acetylcholinesterase. Part II: Interactions with the Catalytic Anionic Site (CAS)

Toxins (Basel). 2018 Sep 25;10(10):389. doi: 10.3390/toxins10100389.

Abstract

The most common type of aflatoxin (AFT) found in nature is aflatoxin B1 (AFB1). This micotoxin is extremely hepatotoxic and carcinogenic to mammals, with acute and chronic effects. It is believed that this could be related to the capacity of AFB1 and its metabolites in inhibiting the enzyme acetylcholinesterase (AChE). In a previous work, we performed an inedited theoretical investigation on the binding modes of these molecules on the peripheral anionic site (PAS) of human AChE (HssAChE), revealing that the metabolites can also bind in the PAS in the same way as AFB1. Here, we investigated the binding modes of these compounds on the catalytic anionic site (CAS) of HssAChE to compare the affinity of the metabolites for both binding sites as well as verify which is the preferential one. Our results corroborated with experimental studies pointing to AFB1 and its metabolites as mixed-type inhibitors, and pointed to the residues relevant for the stabilization of these compounds on the CAS of HssAChE.

Keywords: acetylcholinesterase; aflatoxin B1; catalytic anionic site; metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Acetylcholinesterase / metabolism*
  • Aflatoxin B1 / chemistry
  • Aflatoxin B1 / metabolism*
  • Catalytic Domain
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / metabolism*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular*

Substances

  • Cholinesterase Inhibitors
  • Aflatoxin B1
  • Acetylcholinesterase