5tun - Revision history

OCA at 13:12, 4 October 2023

OCA — Wed, 04 Oct 2023 13:12:39 GMT

←Older revision		Revision as of 13:12, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5tun' size='340' side='right'caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='5tun' size='340' side='right'caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TUN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TUN FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.62Å</td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~">~~<b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K~~]~~, with EC number [http://www~~.~~brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </span>~~</td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tun OCA], [https://pdbe.org/5tun PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tun RCSB], [https://www.ebi.ac.uk/pdbsum/5tun PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tun ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5tun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tun OCA], [~~http~~://pdbe.org/5tun PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tun RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tun PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tun ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN]] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[~~http~~://omim.org/entry/265800 265800]]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.<ref>PMID:8703060</ref> <ref>PMID:9529353</ref> <ref>PMID:10491211</ref> <ref>PMID:10878663</ref>	+	[https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[https://omim.org/entry/265800 265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.<ref>PMID:8703060</ref> <ref>PMID:9529353</ref> <ref>PMID:10491211</ref> <ref>PMID:10878663</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN]] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.	+	[https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cathepsin K]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Aguda~~, A H~~]]	+	[[Category: Aguda AH]]
-	[[Category: Brayer~~, G D~~]]	+	[[Category: Brayer GD]]
-	[[Category: Bromme, D]]	+	[[Category: Bromme D]]
-	[[Category: Kruglyak, N]]	+	[[Category: Kruglyak N]]
-	[[Category: Law, S]]	+	[[Category: Law S]]
-	[[Category: Nguyen~~, N T]]~~	+	[[Category: Nguyen NT]]
-	~~[[Category: Cathepsin k]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 08:19, 8 January 2020

OCA — Wed, 08 Jan 2020 08:19:41 GMT

←Older revision		Revision as of 08:19, 8 January 2020
Line 1:		Line 1:

	==Crystal structure of uninhibited human Cathepsin K at 1.62 Angstrom resolution==		==Crystal structure of uninhibited human Cathepsin K at 1.62 Angstrom resolution==
-	<StructureSection load='5tun' size='340' side='right' caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>	+	<StructureSection load='5tun' size='340' side='right'caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUN FirstGlance]. <br>		<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUN FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5tun" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5tun" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cathepsin 3D structures\|Cathepsin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	[[Category: Cathepsin K]]		[[Category: Cathepsin K]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Aguda, A H]]		[[Category: Aguda, A H]]
	[[Category: Brayer, G D]]		[[Category: Brayer, G D]]

OCA at 14:27, 6 November 2017

OCA — Mon, 06 Nov 2017 14:27:28 GMT

←Older revision		Revision as of 14:27, 6 November 2017
Line 3:		Line 3:
	<StructureSection load='5tun' size='340' side='right' caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='5tun' size='340' side='right' caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUN FirstGlance]. <br>
-	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </span></td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTSK, CTSO, CTSO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tun OCA], [http://pdbe.org/5tun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tun RCSB], [http://www.ebi.ac.uk/pdbsum/5tun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tun ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tun OCA], [http://pdbe.org/5tun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tun RCSB], [http://www.ebi.ac.uk/pdbsum/5tun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tun ProSAT]</span></td></tr>
	</table>		</table>
Line 25:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Cathepsin K]]		[[Category: Cathepsin K]]
		+	[[Category: Human]]
	[[Category: Aguda, A H]]		[[Category: Aguda, A H]]
	[[Category: Brayer, G D]]		[[Category: Brayer, G D]]

OCA at 10:53, 1 February 2017

OCA — Wed, 01 Feb 2017 10:53:50 GMT

←Older revision		Revision as of 10:53, 1 February 2017
Line 1:		Line 1:

-	==Crystal ~~stucture~~ of uninhibited human Cathepsin K at 1.62 Angstrom resolution==	+	==Crystal structure of uninhibited human Cathepsin K at 1.62 Angstrom resolution==
	<StructureSection load='5tun' size='340' side='right' caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>		<StructureSection load='5tun' size='340' side='right' caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 16:10, 18 January 2017

OCA — Wed, 18 Jan 2017 16:10:44 GMT

←Older revision		Revision as of 16:10, 18 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5tun is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal stucture of uninhibited human Cathepsin K at 1.62 Angstrom resolution==
		+	<StructureSection load='5tun' size='340' side='right' caption='[[5tun]], [[Resolution\|resolution]] 1.62Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5tun]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TUN FirstGlance]. <br>
		+	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tun OCA], [http://pdbe.org/5tun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tun RCSB], [http://www.ebi.ac.uk/pdbsum/5tun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tun ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN]] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[http://omim.org/entry/265800 265800]]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.<ref>PMID:8703060</ref> <ref>PMID:9529353</ref> <ref>PMID:10491211</ref> <ref>PMID:10878663</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN]] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Cathepsin K (CatK) is the predominant mammalian bone-degrading protease and thus an ideal target for anti-osteoporotic drug development. Rodent models of osteoporosis are preferred due to their close reflection of the human disease and their ease of handling, genetic manipulation, and economic affordability. However, large differences in the potency of CatK inhibitors for the mouse/rat versus the human protease orthologues have made it impossible to use rodent models. This is even more of a problem considering that the most advanced CatK inhibitors including odanacatib and balicatib failed in human clinical trials due to side effects and rodent models are not available to investigate the mechanism of these failures. Here, we elucidated the structural elements of the potency differences between mouse and human CatK using odanacatib (ODN). We determined and compared the structures of inhibitor-free mouse CatK (mCatK), human CatK (hCatK) and ODN bound to hCatK. Two structural differences were identified and investigated by mutational analysis. Humanizing subsite 2 in mCatK led to a 5-fold improvement of ODN binding whereas the replacement of Tyr61 in mCatK with Asp resulted in an hCatK with comparable ODN potency. Combining both sites further improved the inhibition of the mCatK variant. Similar results were obtained for balicatib. These findings will allow the generation of transgenic CatK mice that will facilitate the evaluation of CatK inhibitor adverse effects and to explore routes to avoid them.

-	~~Authors: Aguda, A.H~~., ~~Kruglyak~~, N., Nguyen, N~~.T.~~, ~~Law, S.~~, Bromme, D.~~, Brayer, G~~.D.	+	Identification of mouse cathepsin K structural elements that regulate the potency of odanacatib.,Law S, Andrault PM, Aguda A, Nguyen N, Kruglyak N, Brayer G, Bromme D Biochem J. 2017 Jan 3. pii: BCJ20160985. doi: 10.1042/BCJ20160985. PMID:28049758<ref>PMID:28049758</ref>

-	~~Description: Crystal stucture~~ of ~~uninhibited human~~ Cathepsin K ~~at 1.62 Angstrom resolution~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5tun" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cathepsin K]]
		+	[[Category: Aguda, A H]]
		+	[[Category: Brayer, G D]]
	[[Category: Bromme, D]]		[[Category: Bromme, D]]
-	[[Category: Law, S]]
-	[[Category: Brayer, G.D]]
-	[[Category: Nguyen, N.T]]
-	[[Category: Aguda, A.H]]
	[[Category: Kruglyak, N]]		[[Category: Kruglyak, N]]
		+	[[Category: Law, S]]
		+	[[Category: Nguyen, N T]]
		+	[[Category: Cathepsin k]]
		+	[[Category: Hydrolase]]

OCA: Protected "5tun" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 17:53:53 GMT

Protected "5tun" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:53, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5tun is ON HOLD until Paper Publication Authors: Aguda, A.H., Kruglyak, N., Nguyen, N.T., Law, S., Bromme, D., Brayer, G.D. Description: Crystal st...

OCA — Fri, 09 Dec 2016 17:53:52 GMT

New page: '''Unreleased structure''' The entry 5tun is ON HOLD until Paper Publication Authors: Aguda, A.H., Kruglyak, N., Nguyen, N.T., Law, S., Bromme, D., Brayer, G.D. Description: Crystal st...

New page

'''Unreleased structure'''

The entry 5tun is ON HOLD until Paper Publication

Authors: Aguda, A.H., Kruglyak, N., Nguyen, N.T., Law, S., Bromme, D., Brayer, G.D.

Description: Crystal stucture of uninhibited human Cathepsin K at 1.62 Angstrom resolution
[[Category: Unreleased Structures]]
[[Category: Bromme, D]]
[[Category: Law, S]]
[[Category: Brayer, G.D]]
[[Category: Nguyen, N.T]]
[[Category: Aguda, A.H]]
[[Category: Kruglyak, N]]