Decarboxylases as hypothetical targets for actions of organophosphates: Molecular modeling for prediction of hidden and unexpected health threats

被引：3

作者：

Aslanli, Aysel ^{[1
]}

Lyagin, Ilya ^{[1
,2
]}

Efremenko, Elena ^{[1
,2
]}

机构：

[1] Lomonosov Moscow State Univ, Fac Chem, Lenin Hills 1-3, Moscow 119991, Russia

[2] RAS, NM Emanuel Inst Biochem Phys, Kosygin Str 4, Moscow 119334, Russia

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2022年 / 161卷

关键词：

Human decarboxylase; Organophosphorus compound; Pesticide; Chemical warfare agent; Molecular modeling; Computational and predictive toxicity; HISTIDINE-DECARBOXYLASE; GLYPHOSATE; INHIBITION; ACID;

D O I：

10.1016/j.fct.2022.112856

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

The rise of various neurodegenerative disorders are somewhat correlating with the worldwide application of multiple anthropogenic toxicants. Though different possible targets were revealed to date, for example, for organophosphorus compounds (OPs), plenty of questions remain. Several decarboxylases (aromatic amino acid decarboxylase, AADC; histidine decarboxylase, HDC; glutamate decarboxylase, GAD) catalyze the biosynthesis of neurotransmitters and neuromodulators and contain pyridoxal phosphate (PLP) as a cofactor. In the current work, 18 OPs which have different neurotoxicity (chemical warfare agents and pesticides) and can penetrate through the blood-brain barrier, were selected. Then, their possible interaction with these decarboxylases in both apo-and holoforms was revealed using computer modeling methods (molecular docking and dynamics). The main amino acid residues of the enzymes responsible for binding OPs have been identified. Individual substances that are most dangerous from the point of view of a possible negative effect on the activity of several decarboxylases were revealed among studied OPs. Glyphosate should be of special interest, since it is not highly toxic towards serine hydrolases, but may prove to be a strong inhibitor for decarboxylases. Holo-AADC could be the most inhibition-prone enzyme among all those investigated.

引用

页数：12

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