The recombinant catalytic domain of membrane-type matrix metalloproteinase-1 (MT1-MMP) induces activation of progelatinase A and progelatinase A complexed with TIMP-2

FEBS Lett. 1996 Nov 18;397(2-3):277-82. doi: 10.1016/s0014-5793(96)01206-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Gelatinases / metabolism*
  • Kinetics
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / metabolism*
  • Oligopeptides / metabolism
  • Polymerase Chain Reaction
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / pharmacology
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Enzyme Precursors
  • Oligopeptides
  • Protease Inhibitors
  • Proteins
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • progelatinase