Structure-function relationships of phospholipases. II: Charge density distribution and the myotoxicity of presynaptically neurotoxic phospholipases

The charge density distribution of 24 phospholipases A2 has been examined to identify the involvement of charged amino acid residues in the determination of the pharmacological properties of these proteins. There is no characteristic difference between the presynaptically neurotoxic and non-neurotoxic phospholipases, however, presynaptically neurotoxic phospholipases which are also myotoxic have a distinct charge distribution pattern. There is a characteristic cationic site around residues 79-87. This site has a relatively fixed position with respect to the hydrophobic 'neurotoxic' region, on the NH2 terminal side. This cationic region is located on the outer surface in the three-dimensional structure of phospholipase, just before hydrophobic helix E, and is available for interaction with membranes. Such a characteristic region is absent in non-myotoxic phospholipases which are either presynaptically active or inactive. On the other hand, myotoxins, a group of non-enzymatic proteins inducing myotoxicity, also possess such characteristic regions of cationic and hydrophobic sites.