Activity of ternary gelatinase A-TIMP-2-matrix metallo-proteinase complexes.
The progelatinase A-TIMP-2 complex behaves like a Janus. Like TIMP (tissue inhibitor of metalloproteinases) it inhibits active matrix metalloproteinases, and activation with 4-aminophenylmercury acetate leads to a gelatinolytic activity. This activity, however, amounts only to less than 10% of that of free gelatinase A not complexed with TIMP-2. When the progelatinase A-TIMP-2 complex inhibits an active matrix metalloproteinase, a ternary complex is generated. After activation with 4-aminophenylmercury acetate this ternary complex displays a more than tenfold proteolytic activity compared to activated gelatinase A-TIMP-2 complex, thus reaching the activity of free gelatinase A. The activity of the ternary complex is nearly independent from the bound matrix metalloproteinase. When the progelatinase A-TIMP-2 complex is activated at first with 4-aminophenylmercury acetate the generation of the ternary complex is made impossible and not such a significant enhancement of activity is observed. These results suggest that gelatinase A-TIMP-2 complex may be a matrix metalloproteinase of the 'second step': It starts its proteolytic attack after it has switched off the activity of other matrix metalloproteinases.
Deutsches Rheuma-Forschungszentrum Berlin, AG Biochemie, Königswarter Krankenhaus, Germany.
H
H
Kolkenbrock
A
A
Hecker-Kia
D
D
Orgel
W
W
Ruppitsch
N
N
Ulbrich
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D017364:Collagenases / Q000097:blood* / Q000302:isolation & purification; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D018093:Gelatinases / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009504:Neutrophils / Q000201:enzymology; D009842:Oligopeptides; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D012867:Skin / Q000201:enzymology; D013379:Substrate Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2
D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8