MMP 24 (MT5-MMP) catalytic domain
Matrix metalloproteinases (MMPs) are Zn2+- and Ca2+-dependent endopeptidases which function in the turnover of extracellular matrix components . Presently fifteen secreted MMPs and six membrane-types MMPs [2-8] are known to be expressed in humans. Human MT5-MMP consists of 645 amino acid residues with a calculated Mr of 73 238 Da [6, 7]. The enzyme exhibits extensive homology to other membrane-type matrix metalloproteinases. It consists of a prodomain, a catalytic domain, a hemopexin-like domain and a C-terminal sequence with a transmembrane segment. Additional characteristic features are a furin activation motif at the end of the prodomain and an 8 amino acid insertion in the catalytic domain. MT5-MMP is expressed in adult brain, kidney, pancreas and lung [6, 7]. Increased amounts of MT5-MMP transcript have been found in astrocytomas, glioblastomas and in pancreas and lung tumors . MT5-MMP activates progelatinase A (72-kDa type IV procollagenase) [6,7]. A recombinant soluble form of the enzyme degrades gelatin, chondroitin sulfate proteoglycan and dermatan sulfate proteoglycan . The proteolytic activity is inhibited by TIMP-2 . MT5-MMP exhibits a tendency to be shed from cell surface membranes. The full-length ectoenzyme appears to undergo rapid autocatalytic destruction into smaller fragments [6, 9].