3.4.24.87 additional information important role for ADAMTS13 in preventing excessive spontaneous Weibel-Palade body secretion, and in the regulation of leukocyte adhesion and extravasation during inflammation 3.4.24.87 additional information ADAMTS13 binds to CD36, a transmembrane protein of endothelial cells and platelets, i.e. glycoprotein IV, not diminishing the proteolytic activity of ADAMTS13, but providing an anchor for ADAMTS13 on the surface of endothelial cells and platelets 3.4.24.87 additional information ADAMTS13 contains eight thrombospondin type 1 repeats and binds to CD36, a transmembrane protein present on endothelial cells and platelets. CD36 also binds to thrombospondin-2 via three thrombospondin type 1 repeats in a manner competitive to ADAMTS13, overview 3.4.24.87 additional information MDTCS domain modelling and substrate recognition mode analysis, overview 3.4.24.87 additional information proteolysis can occur only once VWF has been unraveled from its globular conformation, either by high fluid shear stress in vivo or in the presence of denaturants in vitro, conditions that are able to promote the exposure of the VWF scissile bond 3.4.24.87 additional information removal of newly released ultralarge-von Willebrand factor strings or bundles anchored on endothelial cells by ADAMTS13 occurs rapidly and efficiently in the presence and in the absence of fluid shear stress, suggesting that the cell-bound ultra large-von Willebrand factor polymers may be preferred substrates for ADAMTS13 3.4.24.87 additional information thrombospondin1 and ADAMTS13 form complexes together in cells and in direct protein binding assays 3.4.24.87 additional information plasmin cleaves and ultimately inactivates the enzyme 3.4.24.87 proteins + H2O - 3.4.24.87 proteins + H2O enzyme is involved in thrombotic thrombocytopenic purpura 3.4.24.87 von Willebrand factor + H2O rapid physiological process that occurs on endothelial surfaces, reduced activity results in thrombotic thrombocytopenic pupura 3.4.24.87 von Willebrand factor + H2O cleavage of the peptide bond Tyr842-Met843 within the A2 domain, enzyme deficiency causes lethal thrombotic thrombocytopenic purpura 3.4.24.87 von Willebrand factor + H2O either congenital or acquired defects of the enzyme lead to thrombotic thromcytopenic purpura, cleavage of the peptide bond bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275 3.4.24.87 von Willebrand factor + H2O large multimeric substrate, cleavage of the peptide bond Tyr842-Met843 within the A2 domain 3.4.24.87 von Willebrand factor + H2O protein from plasma of patients suffering type I von Willebrand disease is more susceptible to proteolysis by the enzyme due to amino acid polymorphism heterozygous at position Tyr/Cys1584, phenotypic parameters, cleavage of the peptide bond Tyr842-Met843 within the A2 domain 3.4.24.87 von Willebrand factor + H2O cleavage of peptide bond Tyr842-Met843 3.4.24.87 von Willebrand factor + H2O - 3.4.24.87 von Willebrand factor + H2O specific for 3.4.24.87 von Willebrand factor + H2O cleavage of peptide bond Tyr842-Met843, large hemostatically active multimers are cleaved to smaller less active forms, increased proteolytic degradation in patients suffering from von Willebrand disease typ 2A 3.4.24.87 von Willebrand factor + H2O cleavage of peptide bond Tyr842-Met843, rapid degradation of multimers to smaller fragments, decreased activity results in bone marrow transplant-associated thrombotic microangiopathy and thrombotic thrombocytopenic pupura 3.4.24.87 von Willebrand factor + H2O decrease of the multimeric pattern of enzyme and decreased activity results in bone marrow transplant-associated thrombotid microangiopathy 3.4.24.87 von Willebrand factor + H2O enzyme deficiency causes lethal thrombotic thrombocytopenic purpura, cleavage of peptide bond Tyr1605-Met1606 resulting in limited platelet accumulation in microvascular thrombi (Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275) 3.4.24.87 von Willebrand factor + H2O the cleavage site is exposed to the enzyme by conformational changes due to shear stress in the plasma, decrease of the multimeric pattern of enzyme and decreased activity results in bone marrow transplant-associated thrombotic microangiopathy, cleavage of peptide bond Tyr842-Met843, large hemostatically active multimers are cleaved to smaller less active forms, increased proteolytic degradation in patients suffering von Willebrand disease typ 2A 3.4.24.87 von Willebrand factor + H2O cleavage of Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275 3.4.24.87 von Willebrand factor + H2O ADAMTS13 cleaves at the peptide bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275 3.4.24.87 von Willebrand factor + H2O ADAMTS13 cleaves the bond Tyr842-Met843 within the A2 domain, i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275 3.4.24.87 von Willebrand factor + H2O amino acid position C1584 is necessary for enhanced von Willebrand factor proteolysis by ADAMTS13 3.4.24.87 von Willebrand factor + H2O ADAMTS13 efficiently cleaves only the Tyr842-Met843 bond within the central A2 domain of multimeric von Willebrand factor (i.e. Tyr1605-Met1606 in von Willebrand factor UniProt Id P04275) 3.4.24.87 von Willebrand factor + H2O a catalysis-deficient ADAMTS13 P475S mutant does not show VWF-induced changes in conformation 3.4.24.87 von Willebrand factor + H2O ADAMTS13 cleaves ultra-large von Willebrand factor multimers 3.4.24.87 von Willebrand factor + H2O cleavage of ultra-large multimers 3.4.24.87 von Willebrand factor + H2O force-induced von Willebrand factor A2 domain unfolding of the substrate facilitates cleavage, using single VWF A1A2A3 tridomain polypeptides, structural destabilization of A1A2A3 was induced by 5- to 80-pN forces 3.4.24.87 von Willebrand factor + H2O persistently elevated levels of von Willebrand factor in plasma during and after liver transplantation, while plasma levels of ADAMTS13 dropp during transplantation 3.4.24.87 von Willebrand factor + H2O specific cleavage of ultra-large von Willebrand factor multimers 3.4.24.87 von Willebrand factor + H2O von Willebrand factor is also susceptible to cleavage by ADAMTS13 when incorporated in a thrombus 3.4.24.87 von Willebrand factor + H2O ADAMTS-13 has thiol reductase activity limited towards von Willebrand factor 3.4.24.87 von Willebrand factor + H2O ADAMTS13 specifically cleaves von Willbrand factor A2 domain between Tyr1605 and Met1606 3.4.24.87 von Willebrand factor + H2O cleavage occurs at strand beta4 (Tyr1605-Met1606) in the structural core of the A2 domain. Ca2+ binding stabilizes the A2 domain and impedes its unfolding, and consequently protects it from cleavage by ADAMTS13 3.4.24.87 von Willebrand factor + H2O the disulfide-bond-reducing activity of ADAMTS-13 prevents covalent lateral association and increased platelet adherence of plasma-type von Willebrand factor multimers induced by high fluid shear stress 3.4.24.87 von Willebrand factor + H2O von Willebrand factor A2 domain unfolding is required for proteolysis by ADAMTS13, the ADAMTS13 cleavage site is at Tyr1605-Met1606 3.4.24.87 von Willebrand factor + H2O rapid physiological process that occurs on endothelial surfaces, activity is reduced by 87-100% in patients with thrombotic thrombocytopenic pupura 3.4.24.87 von Willebrand factor + H2O ADAMTS-13 cleavage of von Willebrand factor strings secreted from stimulated and unstimulated HUVECs occurs at the position 1605-6 of the von Willebrand factor A2 domain 3.4.24.87 von Willebrand factor + H2O ADAMTS-13 cleaves the Tyr1605-Met1606 bond in the VWF A2 domain, mechanisms of VWF recognition, cleavage analysis and kinetics under static and flow conditions, overview 3.4.24.87 von Willebrand factor + H2O ADAMTS-13 cleaves von Willebrand factor (VWF) exclusively at the Tyr1605-Met1606 peptide bond in the A2 domain 3.4.24.87 von Willebrand factor + H2O ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond within the central A2 domain 3.4.24.87 von Willebrand factor + H2O ADAMTS13 cleaves von Willebrand factor at the Tyr1605-Met1606 bond 3.4.24.87 von Willebrand factor + H2O ADAMTS13 cleaves von Willebrand factor to smaller less-active forms 3.4.24.87 von Willebrand factor + H2O ADAMTS13 specifically cleaves von Willebrand factor multimers at the site of the Tyr1605-Met1606 bond of the VWF-A2 domain 3.4.24.87 von Willebrand factor + H2O cleavage at the Tyr1605-Met1606 bond within the van Willebrand factor A2 domain 3.4.24.87 von Willebrand factor + H2O cleavage can also occur at the surface of endothelial cells. ADAMTS13 that is prebound to endothelial cells exhibits increased proteolysis of VWF as compared with ADAMTS13 present only in solution. Thus, cleavage of VWF occurs mainly at the endothelial cell surface 3.4.24.87 von Willebrand factor + H2O cleavage of ultra large von Willebrand multimers into smaller fragments 3.4.24.87 von Willebrand factor + H2O specific cleavage of the long strings of ultra-large von Willebrand factor multimers 3.4.24.87 von Willebrand factor 115 + H2O von Willebrand factor is cleaved at the Tyr1605-Met1606 bond in the von Willebrand factor A2 domain