title: Phospholipase D toxins of brown spider venom convert lysophosphatidylcholine and sphingomyelin to cyclic phosphates.
abstract: Venoms of brown spiders in the genus Loxosceles contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These toxins cleave the substrates sphingomyelin and lysophosphatidylcholine in mammalian tissues, releasing the choline head group. The other products of substrate cleavage have previously been reported to be monoester phospholipids, which would result from substrate hydrolysis. Using (31)P NMR and mass spectrometry we demonstrate that recombinant toxins, as well as whole venoms from diverse Loxosceles species, exclusively catalyze transphosphatidylation rather than hydrolysis, forming cyclic phosphate products from both major substrates. Cyclic phosphates have vastly different biological properties from their monoester counterparts, and they may be relevant to the pathology of brown spider envenomation.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Lajoie
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Zobel-Thropp
authors.forename: Vlad K
authors.initials: VK
authors.lastname: Kumirov
authors.forename: Vahe
authors.initials: V
authors.lastname: Bandarian
authors.forename: Greta J
authors.initials: GJ
authors.lastname: Binford
authors.forename: Matthew H J
authors.initials: MH
authors.lastname: Cordes
mesh_terms: D000818:Animals; D063287:Brown Recluse Spider / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000737:chemistry*; D013058:Mass Spectrometry; D010710:Phosphates / Q000737:chemistry*; D010739:Phospholipase D / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013109:Sphingomyelins / Q000737:chemistry*; D013111:Spider Venoms / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D008244:Lysophosphatidylcholines; D010710:Phosphates; D011994:Recombinant Proteins; D013109:Sphingomyelins; D013111:Spider Venoms; D010739:Phospholipase D