Abstract
We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)] is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.
MeSH terms
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ADAM Proteins
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ADAMTS1 Protein
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ADAMTS4 Protein
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Aggrecans
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Amino Acid Sequence
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Arthritis / drug therapy
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Cartilage / metabolism
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Catalytic Domain
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Cloning, Molecular
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Disintegrins / chemistry
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Disintegrins / metabolism
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Extracellular Matrix Proteins*
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Humans
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Hydroxamic Acids / pharmacology
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Interleukin-1 / pharmacology
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Lectins, C-Type
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Metalloendopeptidases / chemistry*
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Metalloendopeptidases / genetics*
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Metalloendopeptidases / isolation & purification
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Metalloendopeptidases / metabolism
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Molecular Sequence Data
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Procollagen N-Endopeptidase
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Protease Inhibitors / pharmacology
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Protein Sorting Signals
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Proteoglycans / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Analysis
Substances
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Aggrecans
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Disintegrins
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Extracellular Matrix Proteins
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Hydroxamic Acids
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Interleukin-1
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Lectins, C-Type
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Protease Inhibitors
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Protein Sorting Signals
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Proteoglycans
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Recombinant Proteins
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ADAM Proteins
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ADAMTS1 Protein
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ADAMTS1 protein, human
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Metalloendopeptidases
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Procollagen N-Endopeptidase
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ADAMTS4 Protein
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ADAMTS4 protein, human