In-depth analysis into the effects of brown spider venom on mammalian cells reveals detailed chemical mechanism.
Research conducted by the University of Arizona (AZ, USA) in collaboration with Lewis and Clark College (OR, USA) has elucidated on the effects of brown spider venom on mammalian tissue, potentially providing insight into the pathology of brown spider envenomation.
The brown spider, which belongs to the genus Loxosceles, harbors powerful venom that can cause severe dermonecrosis and death in humans. The venom contains phospholipase D enzyme toxins capable of cleaving the substrates sphingomyelin and lysophosphatidylcholine in mammalian tissues, releasing the choline head group. Previously, it was thought that this led to the concomitant formation of monoester phopholipids as a result of hydrolysis.
Using 31P NMR and MS techniques, the team, led by Matthew Cordes, Assistant Professor of Biochemistry at the University of Arizona, demonstrated that recombinant toxins, as well as whole venoms from diverse Loxosceles species, exclusively catalyze transphophatidylation to form cyclic phosphate products from both major substrates, thus contradicting the original understanding of the mechanism.
As cyclic phosphates have vastly different biological properties relative to their monoester counterparts, it was concluded by the team that they may be relevant to the pathology of brown spider envenomation.
“The properties of this cyclic molecule are not well known yet, but knowing that it is being produced by toxins in venoms might heighten interest,’ explains Cordes. ‘Knowing how the protein is actually working and making this cyclic molecule could also lead to better insights on how to inhibit that protein,” he added.
Source: Lajoie DM, Zobel-Thropp PA, Kumirov VK, Bandarian V, Binford GJ, Cordes MH. Phospholipase D toxins of brown spider venom convert lysophosphatidylcholine and sphingomyelin to cyclic phosphates. PLoS ONE 8(8), e72372 (2013); Spider venom reveals new secret.