Batroxobin binds fibrin with higher affinity and promotes clot expansion to a greater extent than thrombin.

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Vu TT, Stafford AR, Leslie BA, Kim PY, Fredenburgh JC, Weitz JI

Batroxobin binds fibrin with higher affinity and promotes clot expansion to a greater extent than thrombin.

J Biol Chem. 2013 Jun 7;288(23):16862-71. doi: 10.1074/jbc.M113.464750. Epub 2013 Apr 23.

PubMed ID
23612970 [ View in PubMed
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Abstract

Batroxobin is a thrombin-like serine protease from the venom of Bothrops atrox moojeni that clots fibrinogen. In contrast to thrombin, which releases fibrinopeptide A and B from the NH2-terminal domains of the Aalpha- and Bbeta-chains of fibrinogen, respectively, batroxobin only releases fibrinopeptide A. Because the mechanism responsible for these differences is unknown, we compared the interactions of batroxobin and thrombin with the predominant gammaA/gammaA isoform of fibrin(ogen) and the gammaA/gamma' variant with an extended gamma-chain. Thrombin binds to the gamma'-chain and forms a higher affinity interaction with gammaA/gamma'-fibrin(ogen) than gammaA/gammaA-fibrin(ogen). In contrast, batroxobin binds both fibrin(ogen) isoforms with similar high affinity (Kd values of about 0.5 muM) even though it does not interact with the gamma'-chain. The batroxobin-binding sites on fibrin(ogen) only partially overlap with those of thrombin because thrombin attenuates, but does not abrogate, the interaction of gammaA/gammaA-fibrinogen with batroxobin. Furthermore, although both thrombin and batroxobin bind to the central E-region of fibrinogen with a Kd value of 2-5 muM, the alpha(17-51) and Bbeta(1-42) regions bind thrombin but not batroxobin. Once bound to fibrin, the capacity of batroxobin to promote fibrin accretion is 18-fold greater than that of thrombin, a finding that may explain the microvascular thrombosis that complicates envenomation by B. atrox moojeni. Therefore, batroxobin binds fibrin(ogen) in a manner distinct from thrombin, which may contribute to its higher affinity interaction, selective fibrinopeptide A release, and prothrombotic properties.

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