Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates

• Autor(a) principal: Chaves-Moreira, Daniele
• Data de Publicação: 2023
• Outros Autores: Gremski, Luiza Helena, de Moraes, Fábio Rogério [UNESP], Vuitika, Larissa, Wille, Ana Carolina Martins, Hernández González, Jorge Enrique [UNESP], Chaim, Olga Meiri, Senff-Ribeiro, Andrea, Arni, Raghuvir Krishnaswamy [UNESP], Veiga, Silvio Sanches
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.3390/toxins15020109; http://hdl.handle.net/11449/249715
• topic: brown spider; Loxosceles intermedia; phospholipase-D substrate; phospholipids; recombinant toxin; venom

Brown spider envenomation results in dermonecrosis, characterized by an intense inflammatory reaction. The principal toxins of brown spider venoms are phospholipase-D isoforms, which interact with different cellular membrane components, degrade phospholipids, and generate bioactive mediators leading to harmful effects. The Loxosceles intermedia phospholipase D, LiRecDT1, possesses a loop that modulates the accessibility to the active site and plays a crucial role in substrate. In vitro and in silico analyses were performed to determine aspects of this enzyme’s substrate preference. Sphingomyelin d18:1/6:0 was the preferred substrate of LiRecDT1 compared to other Sphingomyelins. Lysophosphatidylcholine 16:0/0:0 was preferred among other lysophosphatidylcholines, but much less than Sphingomyelin d18:1/6:0. In contrast, phosphatidylcholine d18:1/16:0 was not cleaved. Thus, the number of carbon atoms in the substrate plays a vital role in determining the optimal activity of this phospholipase-D. The presence of an amide group at C2 plays a key role in recognition and activity. In silico analyses indicated that a subsite containing the aromatic residues Y228 and W230 appears essential for choline recognition by cation-π interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.