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 conta in a conserved MMP catalytic domain and an RRRR motif, It lacks a classic c ysteine 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 C A-MMP after the distinct cysteine array motif, and little is known about it s 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 unusu al finding, a chimera combining the catalytic domain of CA-MMP with the pro domain of stromelysin-3 was constructed to express a fully active enzyme in mammalian cells. Purified CA-MMP catalytic domain expresses proteolytic ac tivity against protein substrates in an MMP inhibitor sensitive fashion. Ta ken together, it is concluded that CA-MMP is an MMP with distinct structure , biochemical properties and evolutionary history that may define a new sub class of the MMP superfamily. (C) 1999 Federation of European Biochemical S ocieties.