title: High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2).
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.
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Huey-Sheng
authors.initials: HS
authors.lastname: Shieh
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Mathis
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Williams
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hills
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Joe F
authors.initials: JF
authors.lastname: Wiese
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Benson
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: James R
authors.initials: JR
authors.lastname: Kiefer
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Marino
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Jeffery N
authors.initials: JN
authors.lastname: Carroll
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Leone
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Malfait
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Arner
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017. Electronic address: micky.d.tortorella@pfizer.com.
authors.forename: Micky D
authors.initials: MD
authors.lastname: Tortorella
authors.affiliation: Pfizer Global Research and Development, St. Louis, Missouri 63017.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Tomasselli
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D000071116:ADAMTS5 Protein; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004795:Enzyme Stability / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013696:Temperature; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human