Theoretical evaluation of the malathion and its chemical derivatives interaction with cytosolic phospholipase A2 from zebrafish

Author(s)

Manzi, Agatha ; De-Carli, Bruno Paes ; Roggero, Airam ; De Moraes, Laila Lucyane Ferreira ; Annunciato, Isabelly ; Belchor, Mariana Novo ; Neto, Daniel Ferreira De Lima ; De Oliveira, Marcos Antonio ; Toyama, Marcos Hikari

• Document type: Journal article
• Source: Chemosphere; v. 311, p. 7-pg., 2023-01-01.

Abstract

Cytosolic phospholipase A2 (cPLA2) belongs to a large family of proteins and plays a crucial role in the regu-lation of arachidonic acid metabolism and inflammation cascade in zebrafish (Danio rerio). This enzyme with a molecular weight of 85 kDa, has two distinct domains. One is the regulatory and calcium-dependent (Ca2+) domain called C2, the other is the catalytic alpha/beta hydrolase Ca2+-independent domain, where serine and aspartic acid catalytic dyad residues are present. We investigated the interaction of malathion and their organophosphate metabolites in the cPLA2 using in silico tools. Molecular docking results showed hydrophobic interactions with the paraoxon and catalytic site residue (Ser 223). Malathion increases intracellular Ca2+ due to endoplasmic reticulum influx which in turn activities phospholipase A2 and arachidonic acid release. Molecular docking and homology modelling of proteins and ligands could be a complementary tool for ecotoxicology and environment pollution assessment. (AU)

• FAPESP's process: 21/03352-1 - Phospholipase A2 enzymatic activity as water quality biomarker
• Grantee: Isabelly Annunciato
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/20291-0 - Characterization of the proinflammatory activity of a new serine protease (cdtsp-2) purified from the total venom of Crotalus durissus terrificus
• Grantee: Marcos Hikari Toyama
• Support Opportunities: Regular Research Grants