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
ADAM Proteins
ADAMTS1 Protein
ADAMTS4 Protein
Aggrecans
Amino Acid Sequence
Arthritis/drug therapy
Cartilage/metabolism
Catalytic Domain
Cloning, Molecular
Disintegrins/chemistry,metabolism
Extracellular Matrix Proteins
Humans
Hydroxamic Acids/pharmacology
Interleukin-1/pharmacology
Lectins, C-Type
Metalloendopeptidases/chemistry,genetics,isolation & purification,metabolism
Molecular Sequence Data
Procollagen N-Endopeptidase
Protease Inhibitors/pharmacology
Protein Sorting Signals
Proteoglycans/metabolism
Recombinant Proteins/chemistry,metabolism
Sequence Analysis
Chemicals
Aggrecans
Disintegrins
Extracellular Matrix Proteins
Hydroxamic Acids
Interleukin-1
Lectins, C-Type
Protease Inhibitors
Protein Sorting Signals
Proteoglycans
Recombinant Proteins
ADAM Proteins
ADAMTS1 Protein
ADAMTS1 protein, human
Metalloendopeptidases
Procollagen N-Endopeptidase
ADAMTS4 Protein
ADAMTS4 protein, human
Authors & Affiliations
28 authors, click to expand affiliations / ORCID
Tortorella M D
Department of Inflammatory Diseases Research, DuPont Pharmaceuticals Company, Wilmington, DE 19880-0400, USA.
Burn T C
Pratta M A
Abbaszade I
Hollis J M
Liu R
Rosenfeld S A
Copeland R A
Decicco C P
Wynn R
Rockwell A
Yang F
Duke J L
Solomon K
George H
Bruckner R
Nagase H
Itoh Y
Ellis D M
Ross H
Wiswall B H
Murphy K
Hillman M C
Hollis G F
Newton R C
Magolda R L
Trzaskos J M
Arner E C