Functional and sequence characterization of agkicetin, a new glycoprotein Ib antagonist isolated from Agkistrodon acutus venom. offf2p4.
A new glycoprotein Ib (GPIb) antagonist, agkicetin, was purified from the venom of Agkistrodon acutus and characterized. It is a disulfide-linked heterodimer consisting subunits of 15 and 14 kDa. The subunits are homologous to each other and to other snake venom proteins of the C-type (Ca(2+)-dependent) lectin superfamily. Agkicetin behaved as a potent antagonist of von Willebrand Factor (vWF)-induced platelet agglutination (IC50 = 12.5 nM) and bound specifically to GPIb of fixed platelets with high affinity (Kd = 38 nM). It did not bind coagulation factor IX and thrombin. Monoclonal antibody against epitope on the N-terminal domain of GPIb competed the binding of agkicetin with platelets. Reduced and alkylated agkicetin lost most of its inhibitory efficacy toward vWF-induced platelet agglutination.
Chen
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YL
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China.
Tsai
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IH
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003435:Crotalid Venoms / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D037102:Lectins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D037181:Lectins, C-Type; D008969:Molecular Sequence Data; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
C031442:Agkistrodon venoms; D003435:Crotalid Venoms; D037102:Lectins; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; C093611:agkicetin