title: Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein.
abstract: The matrix metalloproteinases (MMPs) are a group of enzymes which have the ability to degrade extracellular matrix. They also cleave non-matrix proteins such as myelin basic protein and alpha 1-antitrypsin and they are able to process tumour necrosis factor-alpha (TNF) to its mature form. We have cloned, expressed and purified human macrophage metalloelastase (EC 3.4.24.65), an MMP recognised for its ability to degrade elastin, but whose substrate specificity has not yet been defined. With the exception of type I collagen this enzyme degraded all matrix proteins tested, namely: type IV collagen, type I gelatin, fibronectin, laminin, vitronectin and proteoglycan. It also degraded myelin basic protein, cleaved alpha 1-antitrypsin and released TNF from a pro-TNF fusion protein. Thus, in common with several other MMPs, macrophage metalloelastase has a broad substrate range which extends beyond that of elastin alone.
authors.affiliation: British Biotech Pharmaceuticals Ltd., Cowley, Oxford, UK. chandler@britbio.co.uk
authors.forename: S
authors.initials: S
authors.lastname: Chandler
authors.forename: J
authors.initials: J
authors.lastname: Cossins
authors.forename: J
authors.initials: J
authors.lastname: Lury
authors.forename: G
authors.initials: G
authors.lastname: Wells
mesh_terms: D000818:Animals; D002460:Cell Line; D002813:Chondrosarcoma; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D020781:Matrix Metalloproteinase 1; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D004676:Myelin Basic Protein / Q000378:metabolism*; D017354:Point Mutation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004676:Myelin Basic Protein; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate