Surface screening, molecular modeling and in vitro studies on the interactions of aflatoxin M1 and human enzymes acetyl- and butyrylcholinesterase. (1st August 2019)

• Record Type: Journal Article
• Authors: de Almeida, Joyce S.F.D.; Cavalcante, Samir F.de A.; Dolezal, Rafael; Kuca, Kamil; Musilek, Kamil; Jun, Daniel; França, Tanos C.C.
• Is Part Of: Chemico-biological interactions. Volume 308(2019)
• Page Start: 113
• Page End: 119
• Publication Date: 2019-08-01
• Subjects: Aflatoxin M1 -- Surface screening -- Molecular modeling -- Acetylcholinesterase -- Butyrylcholinesterase; AFM1 Aflatoxin M1 -- AFB1 Aflatoxin B1 -- AChE Acetylcholinesterase -- BChE Butyrylcholinesterase -- SS Surface Screening -- HssAChE Homo sapiens sapiens Acethylcolinesterase -- HssBChE Homo sapiens sapiens Butyrycholinesterase -- MD Molecular Dynamics -- CAS Catalytic Anionic Site -- PAS Peripheral Anionic Site -- RM1 Recife Model 1 -- MVD Molegro Virtual Docker -- L-BFGS Limited-Memory Broyden-Fletcher-Goldfarb-Shanno -- PR Position Restrained -- RMSD Root Mean Square Deviation -- RMSF Root Mean Square Fluctuation -- ACPYPE AnteChamber PYthon Parcer InterfacE -- DTNB 5, 5′-dithio-bis-[2-nitrobenzoic acid] -- ATC Acetylthiocholine iodide -- PB Phosphate Buffer -- BTC Butyrylthiocholine iodide -- SEM Standard Error Mean; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2019.05.022
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: 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 ( Hss AChE) 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 ( Hss BChE) was performed. In vitro inhibition tests on both enzymes were done to support theoretical results. MD simulations suggested the catalytic anionic site of Hss AChE as the preferential binding site for AFM1 and also that this metabolite is not a good inhibitor of Hss BChE, 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. Highlights: Interaction studies of aflatoxin M1 (AFM1) with cholinesterases were presented. AFM1 affinity for acetylcholinesterase is higher than for butyrylcholinesterase. AFM1 inhibits acetylcholinesterase but it does not inhibit butyrylcholinesterase. In vitro studies corroborated molecular modeling studies.