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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\u2019s 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-\u03c0 interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.<\/jats:p>","DOI":"10.3390\/toxins15020109","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T01:33:37Z","timestamp":1675042417000},"page":"109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6562-8817","authenticated-orcid":false,"given":"Daniele","family":"Chaves-Moreira","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Federal University of Paran\u00e1 (UFPR), Curitiba 81531-980, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiza Helena","family":"Gremski","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Federal University of Paran\u00e1 (UFPR), Curitiba 81531-980, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0425-0352","authenticated-orcid":false,"given":"F\u00e1bio Rog\u00e9rio","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Department of Physics, Multi-User Center for Biomolecular Innovation, State University of S\u00e3o Paulo (UNESP), S\u00e3o Paulo 05315-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Vuitika","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Federal University of Paran\u00e1 (UFPR), Curitiba 81531-980, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Carolina Martins","family":"Wille","sequence":"additional","affiliation":[{"name":"Department of Structural and Molecular Biology, State University of Ponta Grossa (UEPG), Ponta Grossa 84030-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-8677","authenticated-orcid":false,"given":"Jorge Enrique","family":"Hern\u00e1ndez Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Physics, Multi-User Center for Biomolecular Innovation, State University of S\u00e3o Paulo (UNESP), S\u00e3o Paulo 05315-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3854-3292","authenticated-orcid":false,"given":"Olga Meiri","family":"Chaim","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Federal University of Paran\u00e1 (UFPR), Curitiba 81531-980, Brazil"},{"name":"Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7967-6307","authenticated-orcid":false,"given":"Andrea","family":"Senff-Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Federal University of Paran\u00e1 (UFPR), Curitiba 81531-980, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-1145","authenticated-orcid":false,"given":"Raghuvir Krishnaswamy","family":"Arni","sequence":"additional","affiliation":[{"name":"Department of Physics, Multi-User Center for Biomolecular Innovation, State University of S\u00e3o Paulo (UNESP), S\u00e3o Paulo 05315-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio Sanches","family":"Veiga","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Federal University of Paran\u00e1 (UFPR), Curitiba 81531-980, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","unstructured":"(2022, September 14). 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