Sequence analysis of Lys49 phospholipase A2 myotoxins: a highly conserved class of proteins

A cDNA clone coding for a putative Lys49 phospholipase A2 myotoxin (ACL myotoxin) from Agkistrodon contortrix laticinctus was isolated from a venom gland library and sequenced. The sequence of the first 40 amino acid residues of the predicted protein matches exactly with the N-terminal sequence of the purified myotoxin. Sequence comparison of the predicted sequence of ACL myotoxin and other Lys49 and Asp49 phospholipase A2 enzymes shows that the Lys49 phospholipase toxins form a highly conserved protein family. In addition to the change at position 49, Lys49 myotoxins have several invariant residues not found in the Asp49 group, like Lys7, Glu12, Thr13, Lys16, Lys78, Lys80, Lys115, and Lys116. There are also some conserved residues in the Asp49 group that are not conserved in the Lys49 group: Tyr28, Gly32, Gly33. Gly53. Lys49 myotoxins also have a Lys-rich region in the C-terminus, which is not present in the Asp49 group. These differences clearly indicate that Lys49 myotoxins comprise a conserved and distinct class of phospholipase A2 enzymes.