We have recently shown that cobra cardiotoxin (CTX), a basic polypeptide with (i0 amino acid residues of three-fingered loop, may bind specifically to het)arin/heparan sulfide (heparin/HS). The binding speciticity is controlled by the charge dislribution near the tip of loop 2 region and CTX may then provide a useflfl template for the design of high affinity heparin-binding polypeptides. Herein we show that relocating a positively charge amino acid residue from Lys-3:3 to Arg-28 may also change its binding speciticity from heparin/tiS to chondroitin/dermatan sulfate (CS/DS). This is demonstrated by the enhanced binding constant of several Arg-28 containing, but Lys-33 lacking, CTX homotogues with CS/DS, as compared with heparin/ttS. Since only CTXs from African spitting , but not Asian non-spitting, cobra venom exhibit specific binding with CS/DS over heparin, the result suggests a novel explanation for the biological activity of CTXs in causing the corneal opacity of the victim via the interaction of CTXs with CS/DS proteoglycans. Cobra CTX may also provide a useful tool in future stndies to dissect cell signaling process involving different GAGs.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology