215 - ADAMTS1

Abstract

This chapter elaborates the structural chemistry and the biological aspects of ADAMTS1. The ADAMTS (ADAM with thrombospondin type I motifs) is a new type of ADAM family, the members of which have both a metalloproteinase domain with a sequence homology to SVMPs and a thrombospondin (TSP) type I motif. ADAMTS1 is a secretorytype metalloproteinase consisting of a proprotein, a metalloproteinase domain, disintegrin-like domain, the first TSP type I motif, a spacer region and C-terminal TSP type 1 submotifs. ADAMTS1 gene was originally isolated as a gene selectively expressed in the colon 26 cachexigenic tumor in vivo . ADAMTSl was first shown to be an active metalloproteinase on the basis of its ability to form a covalent binding complex with α2-macroglobulin. ADAMTS1 contains a zinc-binding motif (HExxHxxxxxHD) and a subsequent Met-turn, which comprises the zinc-binding environment of the reprolysin family. Like the ‘cysteine-switch’ mechanism of the matrix metalloproteinases (MMPs), ADAMTS1 possesses a conserved cysteine residue among the reprolysin family in the proprotein domain that may function to maintain the metalloproteinase in a latent state.