Degradation mechanism of the von Willebrand factor A2 domain by nattokinase
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Updated: May 22, 2026

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Ryuichi Hyakumoto1, Masatomo So1, Ayako Furukawa1
1Graduate School of Agriculture, Kyoto University, Japan.
Abstract:
Von Willebrand factor (vWF) is central to hemostasis, yet its ultralarge multimers promote arterial thrombosis. Nattokinase, a natto-derived serine protease, reduces plasma vWF levels, but the underlying mechanism remains unclear. Here, we show that nattokinase directly cleaves the unstructured vWF73 peptide and the folded vWF A2 domain under static conditions. Mass spectrometry identified Thr1608-Gly1609 as the primary cleavage site, located three residues downstream of the ADAMTS13-targeted Tyr1605-Met1606 bond. Kinetic analysis revealed that nattokinase exhibits a catalytic efficiency (kcat/Km) ~200-fold higher than that of ADAMTS13. Unlike ADAMTS13, which requires shear stress to expose its scissile bond, nattokinase functions independently of substrate unfolding. These results provide molecular evidence for direct vWF A2 domain cleavage by nattokinase, providing mechanistic support for its potential contribution to the antithrombotic effects reported for oral nattokinase.
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