Cobra cardiotoxin and phospholipase A2 as GAG-binding toxins: on the path from structure to cardiotoxicity and inflammation.
키워드
요약
Glycosaminoglycans (GAGs) represent the sulfated carbohydrate moieties of proteoglycans which occur abundantly in tissues of the cardiovascular system. Many proteins bind specifically to GAGs and perform an important role in inflammation, cell proliferation, and blood coagulation processes. Recently, in vitro GAG-binding studies of cardiotoxins (CTXs) and basic phospholipase A(2) (PLA(2)) from cobra venom established the toxins as two new families of GAG-binding proteins. In particular, discontinuous basic residues in beta-sheet CTXs may form a cationic cradle suitable for heparin binding, as in the case of fibronectin module III-13. The binding specificity of beta-sheet proteins to different GAGs can be further enhanced by involving other cationic clusters near the flexible loop of the molecule. Since the three-dimensional structures of many CTXs and PLA(2) are available, these two toxins may serve as models for the elucidation of the molecular recognition of GAG-binding proteins and also as polypeptide templates for further improvement of the binding specificity suitable for future biomedical application. Research along the line of GAG-guided toxicity of cobra venom components may help us to understand the functional role of GAGs and the action mechanism of cobra venom components in the cardiovascular system.