The complex between a tissue inhibitor of metalloproteinases (TIMP-2) and 72-kDa progelatinase is a metalloproteinase inhibitor.
Human rheumatoid synovial cells in culture secrete both 72-kDa progelatinase and a complex consisting of 72-kDa progelatinase and a 24-kDa inhibitor of metalloproteinases, TIMP-2. In addition, the culture medium contains TIMP-1, the classical inhibitor of metalloproteinases, with a molecular mass of 30 kDa. TIMP-1 does not form a complex with free 72-kDa progelatinase. Free progelatinase and progelatinase complexed with TIMP-2 can be activated with the organomercury compound p-aminophenylmercury acetate. The activated complex shows less than 10% the enzyme activity of activated free gelatinase. The progelatinase-TIMP-2 complex could be shown to be an inhibitor for other metalloproteinases, such as gelatinase and collagenase secreted by human rheumatoid synovia fibroblasts, as well as for the corresponding enzymes from human neutrophils.
Kolkenbrock
H
H
Institut für Biochemie, Freie Universität Berlin, Federal Republic of Germany.
Orgel
D
D
Hecker-Kia
A
A
Noack
W
W
Ulbrich
N
N
D001172:Arthritis, Rheumatoid / Q000201:enzymology; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D004792:Enzyme Precursors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D018093:Gelatinases; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000097:blood; D008961:Models, Structural; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology; D010434:Pepsin A / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D013583:Synovial Membrane / Q000201:enzymology; D019716:Tissue Inhibitor of Metalloproteinase-2
D004792:Enzyme Precursors; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase