Exosites in Hypervariable Loops of ADAMTS Spacer Domains control Substrate Recognition and Proteolysis.

ABSTRACT: ADAMTS (A Disintegrin-like and Metalloproteinase domain with Thrombospondin type 1 Motif)-1, -4 and -5 share the abilities to cleave large aggregating proteoglycans including versican and aggrecan. These activities are highly relevant to cardiovascular disease and osteoarthritis and during development. Here, using purified recombinant ADAMTS-1, -4 and -5, we quantify, compare, and define the molecular basis of their versicanase activity. A novel sandwich-ELISA detecting the major versican cleavage fragment was used to determine, for the first time, kinetic constants for versican proteolysis. ADAMTS-5 (k_cat/K_m 35 × 10⁵ M^-1 s^-1) is a more potent (~18-fold) versicanase than ADAMTS-4 (k_cat/K_m 1.86 × 10⁵ M

SUBMITTER: Santamaria S 

PROVIDER: S-EPMC6662762 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature