Metalloprotease domain latency protects ADAMTS13 against broad-spectrum inhibitors of metalloproteases while maintaining activity toward VWF

BACKGROUND: ADAMTS13 is a circulating metalloprotease that cleaves von Willebrand factor (VWF) in a shear-dependent manner. ADAMTS13 is secreted as an active protease but has a long half-life, suggesting that it is resistant to circulating protease inhibitors. These zymogen-like properties indicate that ADAMTS13 exists as a latent protease that is activated by its substrate. OBJECTIVES: To investigate the mechanism of ADAMTS13 latency and …