Biologists at Harvard University and Massachusetts General Hospital have shown that independent, but similar, molecular changes turned a harmless digestive enzyme into a toxin in two unrelated species--a shrew and a lizard--giving each a venomous bite. "The venom is essentially an overactivation of the original digestive enzyme, amplifying its effects," said Dr. Yael T. Aminetzach, lead author of the study. "What had been a mild anticoagulant in the salivary glands of both species has become a much more extreme compound that causes paralysis and death in prey that is bitten." In the first part of the study, Dr. Aminetzach and her colleagues compared a toxin found in the salivary glands of the insectivorous North American shrew (Blarina brevicauda) to its closely related digestive enzyme kallikrein. Dr. Aminetzach found that the specific molecular differences between kallikrein and its toxic descendent are highly localized around the enzyme's active site. "Catalysis is fostered by three specific changes that increase enzyme activity," Dr. Aminetzach said. "The active site is physically opened up, and the loops surrounding it become more flexible. The area around the active site also becomes positively charged, serving to better guide the substrate directly into the active site." To further demonstrate that these molecular changes to kallikrein are related to the evolution of toxicity, Aminetzach explored the evolution of another kallikrein-like toxin in the Mexican beaded lizard (Helodermata horridum) (male and female shown in photo). She found that this toxin, while distinct from the analogous toxin in the shrew, nonetheless exhibits the same catalytic enhancement relative to the original kallikrein enzyme.
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