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lyzed as pools [i.e., Bas(C) vs Bas(P)], they were highly distinctive, which may reflect the unique evolutionary pressures the vipers experienced. Bas(C) venom tended to be relatively enriched in serine proteinases, L-amino acid oxidases, and disintegrins, whereas Bas(P) venoms tended to have higher concentrations of phospholipases (PLA2). “In principle, one can use the venom
Snake venoms are mixtures of enzymes and peptides with medical and evolutionary importance. Venom research can lead to better antivenoms, which are collections of antibodies that can neutralize the toxic effects of snakebites. Venom components sometimes can serve as good medicine, as with captopril, a blood-pressure-lowering medication based on a pitviper peptide. Finally, snake venom can help classify and track evolutionary relationships among snake species. But first, researchers must figure out what snake venom comprises. In JPR (DOI 10.1021/ pr800332p), Juan Calvete and colleagues of the Spanish National Research Council (known as CSIC) and the University of Costa Rica tackle the proteomics of snake venom (which they term “snake venomics”) from Slithering into the “venome”. B. asper in the wild. two geographically segregated populations of Costa Rican lancehead pit vipers (Bothrops HPLC profile [of a single snake] to asper). identify whether this snake comes from Costa Rica is bisected northwest-toone part of the country or another,” southeast by a series of mountain says Calvete. ranges. B. asper lives on either side of Second, individual venom heterogethe ranges—one of which faces the neity within a given geographic region Caribbean Sea and the other, the Pais high. So, although a given Caribbean cific Oceansyet herpetologists have snake’s venom is more similar to that long recognized that the effects of a of another Bas(C) snake than to that of snakebite from the two populations a Bas(P) snake, the relative abundance differ. Snakebites from juvenile and of each component varies. That obseradult snakes also differ, with juvenile vation has practical significance, says venom typically causing a more hemCalvete. “If you want to produce an orrhagic wound. antiserum effective against B. asper To figure out why these variations from the Caribbean part or from the exist, the researchers in Costa Rica colPacific part, you need to mix enough lected venom from 15 B. asper specivenom from enough different individumens from the Caribbean side of the als to have something that is statisticountry [called Bas(C)] and 11 from the cally significant for all the individuals.” Pacific side [Bas(P)]. Calvete and his Finally, the team learned that as juteam separated the venom proteins by veniles mature, venom composition reversed-phase HPLC and then subshifts. Juveniles express greater jected each fraction to “a combination amounts of class-3 snake venom metof classical protein chemical methods alloproteinases (PIII-SVMPs) and acidic and modern proteomics,” says Calvete. D49-PLA2, whereas adults produce The analysis yielded three conclugreater amounts of PI-SVMPs and K49sions, says Calvete. First, when venoms PLA2. These results explain previous from the two populations were anafindings that venoms from newborn B.
10.1021/pr800479x
© 2008 American Chemical Society
asper (whether Caribbean or Pacific) are more lethal and tend to induce bleeding and proteolysis, whereas those of adult specimens destroy both blood cells and muscle tissue. “We are giving molecular ground to this observation,” Calvete says. Calvete’s team has investigated North American rattlesnakes, Tunisian and African Gaboon vipers, and Central and South American pit vipers. All of the projects have had shared goals. “On one hand, we want to understand in more detail what is in the venoms of snakes, the mechanisms used by nature to recruit and transform an ordinary protein into a deadly toxin, and how snake venoms evolved,” Calvete says. “Venoms are complex mixtures of proteins that exhibit certain pharmacological properties and kill prey, but they can also be of biomedical interest, a factory of biomaterials.” Toward that end, he is now pursuing the venom-gland transcriptome. That is because no snake genomes have yet been sequenced. As a result, although Calvete and colleagues can sequence peptides, they do not know the gene sequences from which the peptides arise. “For this, we need another approach, and that is to sequence all the mRNAs that code for these proteins, and these are produced in the venom glands.” Once that is done, Calvete will use bioinformatics to identify common antigenic epitopes within each venom protein family. The goal is to make generic synthetic antisera that show greater specificity and efficacy than conventional antivenoms do. “If you are able to design an antibody against a common epitope present in all the isoforms, you can block all the activity in the family,” he explains. “So in principle, you need very few antibodies against each of these protein families to have an effective antivenom, but this is [a] theory,” he says. Calvete’s team plans to test whether this theory holds true. —Jeffrey M. Perkel ALBERTO ALAPE GIRÓN, UNIVERSITY OF COSTA RICA
Snake venomics uncoils venom composition, evolution
Journal of Proteome Research • Vol. 7, No. 8, 2008 3067
