TY - JOUR
T1 - Glycosaminoglycans bind to homologous cardiotoxins with different specificity
AU - Vyas, Kavita A.
AU - Patel, Himatkumar V.
AU - Vyas, Alka A.
AU - Wu, Wen Guey
PY - 1998/3/31
Y1 - 1998/3/31
N2 - We have reported that some cardiotoxins (CTXs), homologous basic polypeptides of cobra venom, bind strongly to heparin. Herein we show that CTXs from spitting cobra venom bind avidly to chondroitin-6-sulfate (CS6) and dermatan sulfate (DS), the glycosaminoglycans (GAGs) abounding in the cornea and elsewhere. We compared the binding strength of Tγ, a major component of spitting cobra, Naja nigricollis, venom with that of CTX A3, a major component of Naja atra venom to various GAGs including CS6, chondroitin-4- sulfate (CS4), DS, keratan sulfate (KS), hyaluronan (HYA), and heparin. The binding strength of Tγ followed the order CS6 > KS > HYA > DS > CS4 > heparin, whereas that of CTX A3 was heparin > KS > CS4 > DS > CS6 > HYA. The binding specificity displayed by different CTXs toward GAGs is impressive, given the high homology among CTXs and among GAGs. Strong binding of Tγ to CS6, rather than to the highly anionic and versatile cousin, heparin, implies specific interaction with CS6. Heparin, at high concentration, displaced CS6 from CS6-Tγ and CS6-A3 complexes. We also show that corneal CS/DS likely allow Tγ to bind to corneal epithelium. CTXs of spitting cobra venom are known to cause corneal opacity and/or blindness. Taken together with these observations, our results suggest that corneal CS/DS play a role in the action of CTX in the eye. Most importantly, the present results establish CTXs as cationic, readily available, avidly binding ligands of CS/DS.
AB - We have reported that some cardiotoxins (CTXs), homologous basic polypeptides of cobra venom, bind strongly to heparin. Herein we show that CTXs from spitting cobra venom bind avidly to chondroitin-6-sulfate (CS6) and dermatan sulfate (DS), the glycosaminoglycans (GAGs) abounding in the cornea and elsewhere. We compared the binding strength of Tγ, a major component of spitting cobra, Naja nigricollis, venom with that of CTX A3, a major component of Naja atra venom to various GAGs including CS6, chondroitin-4- sulfate (CS4), DS, keratan sulfate (KS), hyaluronan (HYA), and heparin. The binding strength of Tγ followed the order CS6 > KS > HYA > DS > CS4 > heparin, whereas that of CTX A3 was heparin > KS > CS4 > DS > CS6 > HYA. The binding specificity displayed by different CTXs toward GAGs is impressive, given the high homology among CTXs and among GAGs. Strong binding of Tγ to CS6, rather than to the highly anionic and versatile cousin, heparin, implies specific interaction with CS6. Heparin, at high concentration, displaced CS6 from CS6-Tγ and CS6-A3 complexes. We also show that corneal CS/DS likely allow Tγ to bind to corneal epithelium. CTXs of spitting cobra venom are known to cause corneal opacity and/or blindness. Taken together with these observations, our results suggest that corneal CS/DS play a role in the action of CTX in the eye. Most importantly, the present results establish CTXs as cationic, readily available, avidly binding ligands of CS/DS.
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U2 - 10.1021/bi972637+
DO - 10.1021/bi972637+
M3 - Article
C2 - 9521773
AN - SCOPUS:0032584320
SN - 0006-2960
VL - 37
SP - 4527
EP - 4534
JO - Biochemistry
JF - Biochemistry
IS - 13
ER -