Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms,
trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in
loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental
in understanding the functional differences between the class I and II spider PLDs. The crystal
structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive
mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of
the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided
insights into the structural determinants for substrate recognition and binding by class II PLDs.
Keywords: Loxoscele, myo-inositol-1-phosphate, phospholipase D, sphingomyelin.
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