Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders.

The Journal of Biological Chemistry
Daniel M LajoieMatthew H J Cordes

Abstract

Venoms of the sicariid spiders contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These enzymes convert sphingolipid and lysolipid substrates to cyclic phosphates by activating a hydroxyl nucleophile present in both classes of lipid. The most medically relevant substrates are thought to be sphingomyelin and/or lysophosphatidylcholine. To better understand the substrate preference of these toxins, we used (31)P NMR to compare the activity of three related but phylogenetically diverse sicariid toxins against a diverse panel of sphingolipid and lysolipid substrates. Two of the three showed significantly faster turnover of sphingolipids over lysolipids, and all three showed a strong preference for positively charged (choline and/or ethanolamine) over neutral (glycerol and serine) headgroups. Strikingly, however, the enzymes vary widely in their preference for choline, the headgroup of both sphingomyelin and lysophosphatidylcholine, versus ethanolamine. An enzyme from Sicarius terrosus showed a strong preference for ethanolamine over choline, whereas two paralogous enzymes from Loxosceles arizonica either preferred choline or showed no significant preference. Intrigued by the novel su...Continue Reading

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Citations

Dec 23, 2015·BMC Evolutionary Biology·Aurélio PedrosoDenise V Tambourgi
Oct 21, 2015·Toxicon : Official Journal of the International Society on Toxinology·Daniel M Lajoie, Matthew H J Cordes
May 29, 2016·Biochimica Et Biophysica Acta·L VuitikaS S Veiga
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Feb 15, 2017·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Daniele Chaves-MoreiraSilvio Sanches Veiga
Dec 20, 2018·BMC Evolutionary Biology·Matthew H J Cordes, Greta J Binford
Mar 12, 2020·Toxins·Luiza Helena GremskiSilvio Sanches Veiga
Jan 18, 2020·Scientific Reports·Amy S FindlayIan J Jackson
Feb 19, 2021·FEBS Open Bio·Takayuki OyamaDaisuke Sugimori
Nov 15, 2019·Toxicon : Official Journal of the International Society on Toxinology·Bárbara Bruna Ribeiro de Oliveira-MendesCarolina Campolina Rebello Horta
Oct 12, 2021·International Journal of Biological Macromolecules·Nayanne Louise Costacurta PolliLuiza Helena Gremski

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