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Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates

Authors :
Daniele Chaves-Moreira
Luiza Helena Gremski
Fábio Rogério de Moraes
Larissa Vuitika
Ana Carolina Martins Wille
Jorge Enrique Hernández González
Olga Meiri Chaim
Andrea Senff-Ribeiro
Raghuvir Krishnaswamy Arni
Silvio Sanches Veiga
Source :
Toxins, Vol 15, Iss 2, p 109 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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.

Details

Language :
English
ISSN :
20726651
Volume :
15
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Toxins
Publication Type :
Academic Journal
Accession number :
edsdoj.b6711c81532b44a6a2be7d4b85a023e0
Document Type :
article
Full Text :
https://doi.org/10.3390/toxins15020109