Surface screening, molecular modeling and in vitro studies on the interactions of aflatoxin M1 and human enzymes acetyl- and butyrylcholinesterase.


Laboratory of Molecular Modeling Applied to Chemical and Biological Defense (LMDQB) Military Institute of Engineering, Praça General Tibúrcio 80, Praia Vermelha, Rio de Janeiro, Brazil; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho, 62, Hradec Kralove, Czech Republic. Electronic address: [Email]


Aflatoxin M1 (AFM1) is a mycotoxin produced by Aspergillus fungi and found in contaminated milk, breastfeed and dairy products, being highly toxic and carcinogenic to humans and other mammalian species. It is also produced in the human body as a metabolite of aflatoxin B1 (AFB1), one of the most toxic natural products known. Previous studies have shown that AFM1 is a potential inhibitor of the enzyme acetylcholinesterase (AChE), and therefore, a potential neurotoxic agent. In this work, surface screening (SS) and molecular dynamics (MD) simulation on human acetylcholinesterase AChE (HssAChE) were performed to corroborate literature data regarding preferential binding sites and type of inhibition. Also, an inedited theoretical study on the interactions of AFM1 with human butyrylcholinesterase (HssBChE) was performed. In vitro inhibition tests on both enzymes were done to support theoretical results. MD simulations suggested the catalytic anionic site of HssAChE as the preferential binding site for AFM1 and also that this metabolite is not a good inhibitor of HssBChE, corroborating previous studies. In vitro assays also corroborated molecular modeling studies by showing that AFM1 did not inhibit BChE and was able to inhibit AChE, although not as much as AFB1.


Acetylcholinesterase,Aflatoxin M1,Butyrylcholinesterase,Molecular modeling,Surface screening,