Generation and activity of the ternary gelatinase B/TIMP-1/LMW-stromelysin-1 complex.
Incubation of progelatinase B, isolated from human polymorphonuclear leukocytes, with TIMP-1 leads to the formation of the progelatinase B/TIMP-1 complex. This complex behaves like a Janus in a similar manner as we previously described for the progelatinase A/TIMP-2 complex. It shows the properties of TIMP-1 and is a better inhibitor for gelatinase A than for gelatinase B. Treatment with trypsin leads to activation of the binary complex. The activity, however, amounts only to slightly more than 10% of the activity of free gelatinase B, not complexed with TIMP-1. When the progelatinase B/TIMP-1 complex inhibits an active matrix metalloproteinase, a ternary complex is generated that after activation displays a distinct higher proteolytic activity than the active binary complex. The active binary complex cannot be transformed into the active ternary complex.
Kolkenbrock
H
H
Deutsches Rheuma-Forschungszentrum Berlin, AG Biochemie, Germany.
Orgel
D
D
Hecker-Kia
A
A
Zimmermann
J
J
Ulbrich
N
N
D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D017364:Collagenases / Q000096:biosynthesis / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000096:biosynthesis; D005347:Fibroblasts / Q000201:enzymology; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D006023:Glycoproteins; D046911:Macromolecular Substances; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9