Abstract
Cobra venom consist of three major components: cardiotoxins (CTXs), neurotoxins (NTXs), and phospholipase A2 (PLA2). Unlike the well-known acetylcholine receptors for NTXs, and diacylglecerol phospholipids for PLA2, the primary target of CTXs remains unidentified. The newly identified NMR structure of CTX complexed with heparin derived disaccharide showed the insight for the exploration of CTXs receptor. Both neutrophil PSGL-1 and GPIba are sialomucins, and an analogous anionic/sulfated tyrosine sequence is involved in ligand recognition by both receptors. Similarly, common features are shared by their respective physiological ligands, vWF and P-selectin. Both of these proteins bind heparin, and both are co-localized within the same storage granules of endothelial cells and platelets. Cardiotoxins also have high affinity for heparin. Coexistence of metaloproteinase in snake venom connected the releactions between CTXs and these proteins. A novel cobra venom metaloproteinase, mocarhagin, has been shown to be able to cleave glycoprotein GPIba (15) and mature N-terminus of PSGL-1. Based on this aspect, we tried to explore the interaction of CTXs and these biologically important polypeptides. We therefore synthesized these peptides and initiated the binding study. The results showed that the interaction between CTXs and peptide is about uM range, and the sulfation did not significantly improve to binding strength. Using intrinsic fluorescence experiments helped us to provide the possible interacted region on cardiotoxin. The intrinsic fluorescence data showed that these peptides shared the same binding with heparin derived disaccharide.