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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.

Original publication

DOI

10.1126/science.284.5420.1664

Type

Journal article

Journal

Science

Publication Date

04/06/1999

Volume

284

Pages

1664 - 1666

Keywords

ADAM Proteins, ADAMTS1 Protein, ADAMTS4 Protein, Aggrecans, Amino Acid Sequence, Arthritis, Cartilage, Catalytic Domain, Cloning, Molecular, Disintegrins, Extracellular Matrix Proteins, Humans, Hydroxamic Acids, Interleukin-1, Lectins, C-Type, Metalloendopeptidases, Molecular Sequence Data, Procollagen N-Endopeptidase, Protease Inhibitors, Protein Sorting Signals, Proteoglycans, Recombinant Proteins, Sequence Analysis