Modeling ADAMTS13-von Willebrand Factor interaction: Implications for oxidative stress-related cardiovascular diseases and type 2A von Willebrand Disease

► The three-dimensional model of ADAMTS13 metalloprotease domain (M13) was built by homology modeling techniques. ► The model was validated against all known artificial and natural mutations found in M13 sequence. ► The peptide vWF(1604-1607) of von Willebrand factor (vWF) was docked into the protease active site. ► The docking model explains why oxidation of Met1606 to methionine sulfoxide inhibits vWF proteolysis by ADAMTS13. ► The model explains why Val1607Asp mutation in type 2A von Willebrand disease accelerates proteolysis of vWF by ADAMTS13.