title: Progelatinase B forms from human neutrophils. complex formation of monomer/lipocalin with TIMP-1.
abstract: The three forms of neutrophil gelatinase B-monomer, homodimer and monomer/lipocalin complex-, were isolated from phorbolester stimulated neutrophil granulocytes by chromatography on gelatin-Sepharose and heparin-Ultrogel. On average, about 50% of the monomer/lipocalin complex was found to be complexed with TIMP-1. After activation with trypsin monomer, homodimer and monomer/lipocalin complex displayed a specific activity of about 2000 mU/mg towards the substrate N-(2,4)-dinitrophenyl-Pro-Gln-Gly-lle-Ala-Gly-Gln-D-Arg, whereas the monomer/lipocalin/TIMP-1 complex could be activated to a specific activity of only 200 mU/mg. The ternary monomer/lipocalin/TIMP-1 complex behaves like the progelatinase A-TIMP-2 complex and the progelatinase B-TIMP-1 complex in that it is an inhibitor for active metalloproteinases (MMPs) and, after activation, a gelatinase with a pronouncedly reduced activity. When the monomer/lipocalin/TIMP-1 complex inhibits an MMP, a quaternary complex monomer/lipocalin/TIMP-1/MMP is generated which after activation shows a sixfold higher proteolytic activity than the active ternary complex.
authors.affiliation: Deutsches Rheumaforschungszentrum Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kolkenbrock
authors.forename: A
authors.initials: A
authors.lastname: Hecker-Kia
authors.forename: D
authors.initials: D
authors.lastname: Orgel
authors.forename: A
authors.initials: A
authors.lastname: Kinawi
authors.forename: N
authors.initials: N
authors.lastname: Ulbrich
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D002352:Carrier Proteins; D004792:Enzyme Precursors; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9