5z5o - Revision history

OCA at 08:45, 22 November 2023

OCA — Wed, 22 Nov 2023 08:45:55 GMT

←Older revision		Revision as of 08:45, 22 November 2023
Line 1:		Line 1:

	==Structure of Pycnonodysostosis disease related I249T mutant of human cathepsin K==		==Structure of Pycnonodysostosis disease related I249T mutant of human cathepsin K==
-	<StructureSection load='5z5o' size='340' side='right' caption='[[5z5o]], [[Resolution\|resolution]] 1.92Å' scene=''>	+	<StructureSection load='5z5o' size='340' side='right'caption='[[5z5o]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z5o]] is a 2 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=5Z5O OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Z5O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z5o]] is a 2 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=5Z5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z5O FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, ~~<scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.92Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene>~~</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1by8\|1by8]]</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=5z5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5o OCA], [https://pdbe.org/5z5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z5o RCSB], [https://www.ebi.ac.uk/pdbsum/5z5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5o ProSAT]</span></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=5z5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5o OCA], [~~http~~://pdbe.org/5z5o PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5z5o RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5z5o PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5o 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 24:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5z5o" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5z5o" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cathepsin 3D structures\|Cathepsin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Cathepsin K~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Biswas, S]]	+	[[Category: Biswas S]]
-	[[Category: Roy, S]]	+	[[Category: Roy S]]
-	~~[[Category: Bone disorder]]~~	+
-	~~[[Category: Cathepsin k]]~~	+
-	~~[[Category: Cysteine protease]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Lysosomal]]~~	+
-	~~[[Category: Pycnodysostosis~~]]	+

OCA at 07:06, 12 December 2018

OCA — Wed, 12 Dec 2018 07:06:31 GMT

←Older revision		Revision as of 07:06, 12 December 2018
Line 3:		Line 3:
	<StructureSection load='5z5o' size='340' side='right' caption='[[5z5o]], [[Resolution\|resolution]] 1.92Å' scene=''>		<StructureSection load='5z5o' size='340' side='right' caption='[[5z5o]], [[Resolution\|resolution]] 1.92Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z5o]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z5O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z5o]] is a 2 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=5Z5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z5O FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1by8\|1by8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1by8\|1by8]]</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='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=5z5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5o OCA], [http://pdbe.org/5z5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z5o RCSB], [http://www.ebi.ac.uk/pdbsum/5z5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5o 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=5z5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5o OCA], [http://pdbe.org/5z5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z5o RCSB], [http://www.ebi.ac.uk/pdbsum/5z5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5o ProSAT]</span></td></tr>
Line 28:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Cathepsin K]]		[[Category: Cathepsin K]]
		+	[[Category: Human]]
	[[Category: Biswas, S]]		[[Category: Biswas, S]]
	[[Category: Roy, S]]		[[Category: Roy, S]]

OCA at 07:54, 26 September 2018

OCA — Wed, 26 Sep 2018 07:54:00 GMT

←Older revision		Revision as of 07:54, 26 September 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5z5o is ~~ON HOLD~~	+	==Structure of Pycnonodysostosis disease related I249T mutant of human cathepsin K==
		+	<StructureSection load='5z5o' size='340' side='right' caption='[[5z5o]], [[Resolution\|resolution]] 1.92Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5z5o]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z5O FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEB:O-BENZYLSULFONYL-SERINE'>SEB</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1by8\|1by8]]</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=5z5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5o OCA], [http://pdbe.org/5z5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z5o RCSB], [http://www.ebi.ac.uk/pdbsum/5z5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5o 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 ==
		+	Human cathepsin K (CTSK) is a collagenolytic lysosomal cysteine protease that plays an important role in bone turnover. Mutation in CTSK gene is associated with loss of collagenolytic activity of CTSK leading to an autosomal recessive bone disorder called pycnodysostosis. Though a number of pycnodysostotic missense mutations have been reported, underlying mechanism of the disease is not clear. In this study we investigated in vitro six recombinant pycnodysostosis related mutants of human CTSK (G79E, I249T, G243E, G303E, G319C and Q187P). While all the mutants, like wild-type, show similar high level of expression in E. coli, four of them (G79E, G303E, G319C and Q187P) are inactive, unstable and spontaneously degrade during purification process. In contrast, proteolytic/collagenolytic activity, zymogen activation kinetics and stability of G243E and I249T mutants are nominally affected. Crystal structure of I249T at 1.92A resolution shows that the mutation in R-domain causes conformational changes of a surface loop in L-domain though the catalytic cleft remains unaltered. Molecular simulation, normal mode analysis and Fluorescence life time measurement eliminated the possibility that the change in L-domain surface loop orientation is a crystallization artefact. CD-based thermal melting profile indicates that stability of I249T is significantly higher than wild-type. Our studies first time reports that pycnodysostosis are not always correlated with either a complete loss of proteolytic activity or at least collagenolytic activity due to mutation of CTSK gene. The first crystal structure of a pycnodysostotic mutant (I249T) provides critical information that may pave new avenues towards understanding the disease at molecular level. This article is protected by copyright. All rights reserved.

-	~~Authors~~: ~~Biswas, S~~., Roy, S.	+	Not all pycnodysostosis-related mutants of human cathepsin K are inactive: Crystal structure and biochemical studies of an active mutant I249T.,Roy S, Das Chakraborty S, Biswas S FEBS J. 2018 Sep 10. doi: 10.1111/febs.14655. PMID:30199612<ref>PMID:30199612</ref>

-	~~Description: Structure~~ of ~~Pycnonodysostosis disease related I249T mutant~~ of ~~human cathepsin K~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Roy, S~~]]	+	<div class="pdbe-citations 5z5o" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cathepsin K]]
	[[Category: Biswas, S]]		[[Category: Biswas, S]]
		+	[[Category: Roy, S]]
		+	[[Category: Bone disorder]]
		+	[[Category: Cathepsin k]]
		+	[[Category: Cysteine protease]]
		+	[[Category: Hydrolase]]
		+	[[Category: Lysosomal]]
		+	[[Category: Pycnodysostosis]]

OCA: Protected "5z5o" [edit=sysop:move=sysop]

OCA — Wed, 24 Jan 2018 17:12:52 GMT

Protected "5z5o" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:12, 24 January 2018

OCA: New page: '''Unreleased structure''' The entry 5z5o is ON HOLD Authors: Biswas, S., Roy, S. Description: Structure of Pycnonodysostosis disease related I249T mutant of human cathepsin K [[Catego...

OCA — Wed, 24 Jan 2018 17:12:51 GMT

New page: '''Unreleased structure''' The entry 5z5o is ON HOLD Authors: Biswas, S., Roy, S. Description: Structure of Pycnonodysostosis disease related I249T mutant of human cathepsin K [[Catego...

New page

'''Unreleased structure'''

The entry 5z5o is ON HOLD

Authors: Biswas, S., Roy, S.

Description: Structure of Pycnonodysostosis disease related I249T mutant of human cathepsin K
[[Category: Unreleased Structures]]
[[Category: Roy, S]]
[[Category: Biswas, S]]