Computational interaction analysis of organophosphorus pesticides with different metabolic proteins in humans

Abstract

Pesticides have the potential to leave harmful effects on humans, animals, other living organisms, and the environment. Several human metabolic proteins inhibited after exposure to organophosphorus pesticides absorbed through the skin, inhalation, eyes and oral mucosa, are most important targets for this interaction study. The crystal structure of five different proteins, PDBIDs: 3LII, 3NXU, 4GTU, 2XJ1 and 1YXA in Homo sapiens (H. sapiens), interact with organophosphorus pesticides at the molecular level. The 3-D structures were found to be of good quality and validated through PROCHECK, ERRAT and ProSA servers. The results show that the binding energy is maximum -45.21 relative units of cytochrome P450 protein with phosmet pesticide. In terms of H-bonding, methyl parathion and parathion with acetylcholinesterase protein, parathion, methylparathion and phosmet with protein kinase C show the highest interaction. We conclude that these organophosphorus pesticides are more toxic and inhibit enzymatic activity by interrupting the metabolic pathways in H. sapiens.

Keywords: Homo sapiens; acetylcholinesterases; comparative analysis; docking; modeling; organophosphorus pesticides; toxicity analysis.

Fig. 1. The overall quality score (E-value) of A, B, C, D, E represents AchE, P450, GST, PKC and ACT proteins respectively by using ERRAT server.

Fig. 2. Secondary structure of five different human proteins.

A: human acetylcholinesterase (3LII). B: cytochromeP450 (3NXU). C: gutathione S-transferase (4GTU). D: represents protein kinase C (2XJ1). E: is alpha-1-antichymotrypsin (1YXA). The arrow indicates the β-sheets with flexible residues shown in yellow, α-helices in red color and green are the loop regions. The protein structures were visualized through PyMol V2.0.7.

Fig. 3. Comparative analysis of functional assignment of five different human proteins by SVMProt method through BIDD server.

A: acetylcholinesterase. B: cytochrome P450. C: gutathione S-transferase. D: protein kinase C. E: alpha-1-antichymotrypsin proteins.

Fig. 4. The possible binding sites which were obtained by using CASTp server of all five proteins in human.

A: human acetylcholinesterase (3LII). B: cytochrome P450 (3NXU). C: gutathione S-transferase (4GTU). D: protein kinase C (2XJ1). E: α-1-antichymotrypsin (1YXA). The possible binding site indicates in various colors like blue, green, cyan, etc.

Fig. 5. The graphical plot shows the global energy i.e. dock score of five different metabolic proteins i.e. acetylcholinesterase (AchE), cytochrome P450 (P450), glutathione S-transferases (GST), protein kinase C (PCK) and α-1-antichymotrypsin (ACT) with ten different organophosphorous pesticides.

Fig. 6. Molecular docking through PatchDock and refined by FireDock.

A: It represent the acetylcholinesterase (Pdbid: 3LII) with parathion pesticides and dock score is -37.90. B: The highest binding energy is -45.21 of cytochrome P450 protein (Pdbid: 3NXU) with phosmet. C: Similarly, the glutathione S-tranferase (Pdbid: 4GTU) with ligand as an azinphosmethyl pesticides and score is -39.60. D: Binding energy -36.57 of protein kinase C (Pdbid: 2XJ1) with azinphosmethyl. E: Alpha-1-antichymotrypsin (Pdbid: 1YXA) with quinalphos are -30.15. Structures were visualized using PyMol V2.0.7 software viewer.