An overview of lysine-49 phospholipase A2 myotoxins from crotalid snake venoms and their structural determinants of myotoxic action.
In 1984, the first venom phospholipase A2 (PLA2) with a lysine substituting for the highly conserved aspartate 49 was discovered, in the North American crotalid snake Agkistrodon p. piscivorus [J. Biol. Chem. 259 (1984) 13839]. Ten years later, the first mapping of a 'toxic region' on a Lys49 PLA2 was reported, in Bothrops asper myotoxin II [J. Biol. Chem. 269 (1994) 29867]. After a further decade of research on the Lys49 PLA2s, a better understanding of their structural determinants of toxicity and mode of action is rapidly emerging, with myotoxic effector sites identified at the C-terminal region in at least four proteins: B. asper myotoxin II, A. p. piscivorus K49 PLA2, A. c. laticinctus ACL myotoxin, and B. jararacussu bothropstoxin I. Although important features still remain to be established, their toxic mode of action has now been understood in its more general concepts, and a consistent working hypothesis can be experimentally supported. It is proposed that all the toxic activities of Lys49 PLA2s are related to their ability to destabilize natural (eukaryotic and prokaryotic) and artificial membranes, using a cationic/hydrophobic effector site located at their C-terminal loop. This review summarizes the general properties of the Lys49 PLA2 myotoxins, emphasizing the development of current concepts and hypotheses concerning the molecular basis of their toxic activities.
Lomonte
Bruno
B
Facultad de Microbiología, Instituto Clodomiro Picado, Universidad de Costa Rica, San José, Costa Rica. blomonte@cariari.ucr.ac.cr
Angulo
Yamileth
Y
Calderón
Leonel
L
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017837:Bothrops / Q000235:genetics* / Q000378:metabolism; D003435:Crotalid Venoms / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D008566:Membranes / Q000187:drug effects*; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics*; D010741:Phospholipases A / Q000737:chemistry* / Q000235:genetics; D054467:Phospholipases A2; D011487:Protein Conformation
D003435:Crotalid Venoms; D010741:Phospholipases A; D054467:Phospholipases A2