2rjq
Crystal structure of ADAMTS5 with inhibitor bound
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| , resolution 2.600Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | ADAMTS5, ADAMTS11, ADMP2 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
Aggrecanases are now believed to be the principal proteinases responsible for aggrecan degradation in osteoarthritis. Given their potential as a drug target, we solved crystal structures of the two most active human aggrecanase isoforms, ADAMTS4 and ADAMTS5, each in complex with bound inhibitor and one wherein the enzyme is in apo form. These structures show that the unliganded and inhibitor-bound enzymes exhibit two essentially different catalytic-site configurations: an autoinhibited, nonbinding, closed form and an open, binding form. On this basis, we propose that mature aggrecanases exist as an ensemble of at least two isomers, only one of which is proteolytically active.
About this StructureAbout this Structure
2RJQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5., Mosyak L, Georgiadis K, Shane T, Svenson K, Hebert T, McDonagh T, Mackie S, Olland S, Lin L, Zhong X, Kriz R, Reifenberg EL, Collins-Racie LA, Corcoran C, Freeman B, Zollner R, Marvell T, Vera M, Sum PE, Lavallie ER, Stahl M, Somers W, Protein Sci. 2008 Jan;17(1):16-21. Epub 2007 Nov 27. PMID:18042673
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