The recombinant catalytic domain of membrane-type matrix metalloproteinase-1 (MT1-MMP) induces activation of progelatinase A and progelatinase A complexed with TIMP-2.
A truncated form of the membrane-type matrix metalloproteinase-1 [(Ala21-Ile318)proMT1-MMP] lacking the hemopexin-like and trans-membrane domain was produced in E. coli. We demonstrate that the recombinant proenzyme was autoproteolytically processed to a fully active catalytic domain with N-terminal Ile114. The catalytic domain of MT1-MMP initiated the activation of progelatinase A and progelatinase A complexed with tissue inhibitor of metalloproteinases-2 (TIMP-2). As a typical soluble metalloproteinase it was able to cleave physiologic as well as synthetic substrates. Our kinetic data demonstrate that TIMP-2 is a potent inhibitor for the recombinant enzyme.
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Universität Bielefeld, Fakultät für Chemie, Abteilung Biochemie I, Bielefeld, Germany.
Kolkenbrock
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Tschesche
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D001665:Binding Sites; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D018093:Gelatinases / Q000378:metabolism*; D007700:Kinetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2
D004792:Enzyme Precursors; D009842:Oligopeptides; D011480:Protease Inhibitors; D011506:Proteins; D011994:Recombinant Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase