Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins.
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.
Tortorella
M D
MD
Department of Inflammatory Diseases Research, DuPont Pharmaceuticals Company, Wilmington, DE 19880-0400, USA.
Burn
T C
TC
Pratta
M A
MA
Abbaszade
I
I
Hollis
J M
JM
Liu
R
R
Rosenfeld
S A
SA
Copeland
R A
RA
Decicco
C P
CP
Wynn
R
R
Rockwell
A
A
Yang
F
F
Duke
J L
JL
Solomon
K
K
George
H
H
Bruckner
R
R
Nagase
H
H
Itoh
Y
Y
Ellis
D M
DM
Ross
H
H
Wiswall
B H
BH
Murphy
K
K
Hillman
M C
MC
Hollis
G F
GF
Newton
R C
RC
Magolda
R L
RL
Trzaskos
J M
JM
Arner
E C
EC
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D053674:Aggrecans; D000595:Amino Acid Sequence; D001168:Arthritis / Q000188:drug therapy; D002356:Cartilage / Q000378:metabolism; D020134:Catalytic Domain; D003001:Cloning, Molecular; D019483:Disintegrins / Q000737:chemistry / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D037181:Lectins, C-Type; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D011348:Procollagen N-Endopeptidase; D011480:Protease Inhibitors / Q000494:pharmacology; D021382:Protein Sorting Signals; D011509:Proteoglycans / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017421:Sequence Analysis
D053674:Aggrecans; D019483:Disintegrins; D016326:Extracellular Matrix Proteins; D006877:Hydroxamic Acids; D007375:Interleukin-1; D037181:Lectins, C-Type; D011480:Protease Inhibitors; D021382:Protein Sorting Signals; D011509:Proteoglycans; D011994:Recombinant Proteins; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D008666:Metalloendopeptidases; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human