CLONING OF 3 CAENORHABDITIS-ELEGANS GENES POTENTIALLY ENCODING NOVEL MATRIX METALLOPROTEINASES

Three genes potentially encoding novel matrix metalloproteinases (MMPs ) were identified by sequence similarity searching of Caenorhabditis e legans genome database, and cDNAs for these MMPs were cloned. The pred icted gene products (MMP-C31, -H19 and -Y19) display a similar domain organization to human MMPs. MMP-H19 and -Y19 are unique in that they h ave an RXKR motif between the propeptide and catalytic domains that is a furin-like cleavage site, and conserved only in stromelysin-3 and m embrane-type MMPs. The amino acid sequence homology with MMP-1/human i nterstitial collagenase at the catalytic domain is 45%, 34% and 23% fo r MMP-C31, -H19 and -Y19, respectively. Recombinant proteins of C. ele gans MMPs cleaved an MMP peptide substrate with efficiency proportiona l to their amino acid homology with human MMPs. Digestion of gelatin w as observed only with MMP-C31. Enzyme activity of MMP-C31 and -H19 was inhibited by human tissue inhibitor of MMPs (TIMP)-1, TIMP-2 and synt hetic MMP inhibitors, BB94 and CT543, indicating that the catalytic si tes of these C. elegans MMPs are structurally closely related with tho se of mammalian MMPs. (C) 1998 Elsevier Science B.V. All rights reserv ed.