2rjp: Difference between revisions

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==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.

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==

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==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;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042673 18042673]

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: Homo sapiens]]

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[[Category: zymogen]]

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@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 10: / Line 10: @@
 ==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;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18042673 18042673]
+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: Homo sapiens]]
@@ Line 32: / Line 32: @@
 [[Category: zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:13:32 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:47:53 2008''