High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2).
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.
Shieh
Huey-Sheng
HS
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Mathis
Karl J
KJ
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Williams
Jennifer M
JM
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Hills
Robert L
RL
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Wiese
Joe F
JF
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Benson
Timothy E
TE
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Kiefer
James R
JR
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Marino
Margaret H
MH
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Carroll
Jeffery N
JN
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Leone
Joseph W
JW
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Malfait
Anne-Marie
AM
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Arner
Elizabeth C
EC
Pfizer Global Research and Development, St. Louis, Missouri 63017.
Tortorella
Micky D
MD
Pfizer Global Research and Development, St. Louis, Missouri 63017. Electronic address: micky.d.tortorella@pfizer.com.
Tomasselli
Alfredo
A
Pfizer Global Research and Development, St. Louis, Missouri 63017.
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
D004791:Enzyme Inhibitors; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human