Abstract
Aggrecanase-2 (a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5)), a member of the ADAMTS protein family, is critically involved in arthritic diseases because of its direct role in cleaving the cartilage component aggrecan. The catalytic domain of aggrecanase-2 has been refolded, purified, and crystallized, and its three-dimensional structure determined to 1.4A resolution in the presence of an inhibitor. A high resolution structure of an ADAMTS/aggrecanase protein provides an opportunity for the development of therapeutics to treat osteoarthritis.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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ADAM Proteins / antagonists & inhibitors
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ADAM Proteins / chemistry*
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ADAM Proteins / isolation & purification
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ADAM Proteins / metabolism
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ADAMTS5 Protein
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Amino Acid Sequence
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Catalytic Domain*
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Crystallography, X-Ray
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Enzyme Inhibitors / pharmacology
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Enzyme Stability / drug effects
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Humans
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Models, Molecular
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Molecular Sequence Data
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Protein Folding
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Protein Structure, Secondary
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Temperature
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Tissue Inhibitor of Metalloproteinase-3 / metabolism
Substances
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Enzyme Inhibitors
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Tissue Inhibitor of Metalloproteinase-3
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ADAM Proteins
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ADAMTS5 Protein
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ADAMTS5 protein, human