The C-terminal domain of 72 kDa gelatinase A is not required for catalysis, but is essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases

Biochem J. 1992 May 1;283 ( Pt 3)(Pt 3):637-41. doi: 10.1042/bj2830637.

Abstract

Recombinant 72 kDa gelatinase A and a truncated form lacking the C-terminal domain were shown to be activated by organomercurials and to possess similar activities towards a number of substrates. The truncated proenzyme differed from the full-length gelatinase in that it could not be activated by a membrane activator and did not bind tissue inhibitor of metalloproteinase (TIMP)-2. Kinetic studies also showed that the inhibition of the activated truncated enzyme, by both TIMP-1 and TIMP-2, was considerably decreased compared with the full-length enzyme. We conclude that the C-terminal domain plays an important role in the regulation of gelatinase A by a potential physiological activator and inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Catalysis
  • Cell Membrane / enzymology
  • DNA / chemistry
  • Enzyme Activation
  • Gelatinases
  • Glycoproteins / metabolism
  • Glycoproteins / pharmacology
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Molecular Weight
  • Mutagenesis
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / pharmacology
  • Pepsin A / chemistry
  • Pepsin A / genetics
  • Pepsin A / metabolism*
  • Peptide Fragments / metabolism*
  • Structure-Activity Relationship
  • Tissue Inhibitor of Metalloproteinase-2
  • Tissue Inhibitor of Metalloproteinases

Substances

  • Glycoproteins
  • Neoplasm Proteins
  • Peptide Fragments
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • DNA
  • Pepsin A
  • Gelatinases