Autor(es)

Chaves-Moreira, Daniele ; Gremski, Luiza Helena ; de Moraes, Fabio Rogerio ; Vuitika, Larissa ; Martins Wille, Ana Carolina ; Hernandez Gonzalez, Jorge Enrique ; Chaim, Olga Meiri ; Senff-Ribeiro, Andrea ; Arni, Raghuvir Krishnaswamy ; Veiga, Silvio Sanches

• Tipo de documento: Artigo Científico
• Fonte: TOXINS; v. 15, n. 2, p. 17-pg., 2023-02-01.

Resumo

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-pi interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms. (AU)

• Processo FAPESP: 20/08615-8 - Exosítios de proteínas, sítios crípticos e moonlighting: identificação, mapeamento funcional e efeitos de alteração estrutural.
• Beneficiário: Raghuvir Krishnaswamy Arni
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/10214-1 - Estratégias computacionais e experimentais integradas para a inibição das toxinas exfoliativas de Staphylococcus aureus
• Beneficiário: Jorge Enrique Hernández González
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado