Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases.
Three genes potentially encoding novel matrix metalloproteinases (MMPs) were identified by sequence similarity searching of Caenorhabditis elegans genome database, and cDNAs for these MMPs were cloned. The predicted gene products (MMP-C31,-H19 and -Y19) display a similar domain organization to human MMPs. MMP-H19 and -Y19 are unique in that they have an RXKR motif between the propeptide and catalytic domains that is a furin-like cleavage site, and conserved only in stromelysin-3 and membrane-type MMPs. The amino acid sequence homology with MMP-1/human interstitial collagenase at the catalytic domain is 45%, 34% and 23% for MMP-C31, -H19 and -Y19, respectively. Recombinant proteins of C. elegans MMPs cleaved an MMP peptide substrate with efficiency proportional to their amino acid homology with human MMPs. Digestion of gelatin was 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 synthetic MMP inhibitors, BB94 and CT543, indicating that the catalytic sites of these C. elegans MMPs are structurally closely related with those of mammalian MMPs.
Wada
K
K
Department of Molecular Virology, Oncology, Cancer Research Institute, Kanazawa University, Kanazawa 920, Japan.
Sato
H
H
Kinoh
H
H
Kajita
M
M
Yamamoto
H
H
Seiki
M
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics; D005780:Gelatin / Q000378:metabolism; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000737:chemistry; D008666:Metalloendopeptidases / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D029742:Caenorhabditis elegans Proteins; D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D011994:Recombinant Proteins; D005780:Gelatin; D008666:Metalloendopeptidases; C112614:ZMP-2 protein, C elegans; C112615:zmp-1 protein, C elegans; C112613:zmp-3 protein, C elegans