The C-terminal mutation beyond the catalytic site of brown spider phospholipase D significantly impacts its biological activities.

Loxosceles spider envenomation results in dermonecrosis, principally due to phospholipases D (PLDs) present in the venom. These enzymes have a strongly conserved sequence, ATXXDNPW, in the C-terminal region (SMD-tail) that make contact with β-sheets of the TIM barrel, in which the amino acids Asp277 and Trp280 establish the energetically strongest contacts. The SMD-tail is conserved in PLDs from different species but absent in the non-toxic PLD ancestral glycerophosphodiester phosphodiesterases (GDPDs).