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.
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.
Murphy
G
G
Strangeways Research Laboratory, Worts Causeway, Cambridge, U.K.
Willenbrock
F
F
Ward
R V
RV
Cockett
M I
MI
Eaton
D
D
Docherty
A J
AJ
D001483:Base Sequence; D002384:Catalysis; D002462:Cell Membrane / Q000201:enzymology; D004247:DNA / Q000737:chemistry; D004789:Enzyme Activation; D018093:Gelatinases; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology; D010434:Pepsin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D013329:Structure-Activity Relationship; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D004247:DNA; D010434:Pepsin A; D018093:Gelatinases