2007Journal of Biological ChemistryOpen access

High Resolution Crystal Structure of the Catalytic Domain of ADAMTS-5 (Aggrecanase-2)

Huey‐Sheng Shieh, Karl J. Mathis, Jennifer M. Williams, Robert L. Hills, Joe F. Wiese, Timothy E. Benson, James R. Kiefer, Margaret H. Marino, Jeffery N. Carroll, Joseph W. Leone, Anne‐Marie Malfait, Elizabeth C. Arner, Micky D. Tortorella, Alfredo G. Tomasselli

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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.

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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.

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Available 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.

Key concepts: Aggrecanase, ADAMTS, Aggrecan, Thrombospondin, Disintegrin, Chemistry, Metalloproteinase, Osteoarthritis

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