Classification of phospholipases A2 according to sequence. Evolutionary and pharmacological implications.

The sequences of 32 phospholipases A2 (EC 3.1.1.4) were systematically compared on the basis of polypeptide chain length and similarity at selected amino acid positions around the active site. Two difference matrices were constructed and the various groupings present in the data were expressed in dendrogram form. The two methods of comparison yielded different results, and this is seen as a consequence of separate aspects of phospholipase evolution being highlighted in each case. It appears that, although Elapid snake venom phospholipases are very similar in terms of overall conformation, the area around their active sites distinguishes them into two major groups, namely the Asian Elapids and the marine/Australasian Elapids. Further, the Asian Elapids seem to have active-site vicinities which are closer to those in the mammalian pancreatic phospholipases. The relevance of the classifications to structure/activity relationships (especially beta-neurotoxicity) and phospholipase evolution is discussed.