CA-MMP: a matrix metalloproteinase with a novel cysteine array, but without the classic cysteine switch

A matrix metalloproteinase (MMP)-like gene was identified in mouse to contain a conserved MMP catalytic domain and an RRRR motif, It lacks a classic cysteine switch, but it possesses two novel motifs: a cysteine array (Cys-X-6-Cys-X-8-Cys-X-10-Cys-X-3-Cys-X-2-Cys), and a novel Ig-fold, It is named CA-MMP after the distinct cysteine array motif, and little is known about its biochemical function. In an attempt to characterize CA-MMP activity, the full-length sequence was expressed in mammalian cells and its product found to be cell-associated without detectable secretion, In light of this unusual finding, a chimera combining the catalytic domain of CA-MMP with the prodomain of stromelysin-3 was constructed to express a fully active enzyme in mammalian cells. Purified CA-MMP catalytic domain expresses proteolytic activity against protein substrates in an MMP inhibitor sensitive fashion. Taken together, it is concluded that CA-MMP is an MMP with distinct structure, biochemical properties and evolutionary history that may define a new subclass of the MMP superfamily. (C) 1999 Federation of European Biochemical Societies.