title: The N-terminal domain of tissue inhibitor of metalloproteinases retains metalloproteinase inhibitory activity.
abstract: Recombinant tissue inhibitor of metalloproteinases (TIMP-1) and a truncated version containing only the three N-terminal loops, delta 127-184TIMP, have been expressed in myeloma cells and purified by affinity chromatography and gel filtration. delta 127-184TIMP was found to exist as two main glycosylation variants of molecular mass 24 kD and 19.5 kDa and an unglycosylated form of 13 kDa. All forms of the truncated inhibitor were able to inhibit and form complexes with active forms of the matrix metalloproteinases, indicating that the major structural features for specific interaction with these enzymes resides in these three loops. Stable binding of delta 127-184TIMP to pro 95-kDa gelatinase was not demonstrable under the conditions for binding of full-length TIMP-1.
authors.affiliation: Strangeways Research Laboratory, Cambridge, U.K.
authors.forename: G
authors.initials: G
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Houbrechts
authors.forename: M I
authors.initials: MI
authors.lastname: Cockett
authors.forename: R A
authors.initials: RA
authors.lastname: Williamson
authors.forename: M
authors.initials: M
authors.lastname: O'Shea
authors.forename: A J
authors.initials: AJ
authors.lastname: Docherty
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D004795:Enzyme Stability; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D046911:Macromolecular Substances; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008969:Molecular Sequence Data; D010954:Plasmacytoma; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured
chemical_list: D006023:Glycoproteins; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases