2rjp
From Proteopedia
(New page: 200px<br /><applet load="2rjp" size="350" color="white" frame="true" align="right" spinBox="true" caption="2rjp, resolution 2.800Å" /> '''Crystal structure o...) |
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==Overview== | ==Overview== | ||
| - | Aggrecanases are now believed to be the principal proteinases responsible | + | 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 Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | 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. 2007 Nov 27 | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042673 18042673] |
[[Category: ADAMTS-4 endopeptidase]] | [[Category: ADAMTS-4 endopeptidase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:47:53 2008'' |
Revision as of 16:47, 21 February 2008
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Crystal structure of ADAMTS4 with inhibitor bound
Overview
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 Structure
2RJP is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as ADAMTS-4 endopeptidase, with EC number 3.4.24.82 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:47:53 2008
Categories: ADAMTS-4 endopeptidase | Homo sapiens | Single protein | Mosyak, L. | Somers, W. | Stahl, M. | 886 | CA | ZN | Aggrecanase | Cleavage on pair of basic residues | Extracellular matrix | Glycoprotein | Hydrolase | Metal-binding | Metalloprotease domain | Polymorphism | Secreted | Zinc | Zymogen
