6qbh - Revision history

OCA at 11:57, 24 January 2024

OCA — Wed, 24 Jan 2024 11:57:12 GMT

←Older revision		Revision as of 11:57, 24 January 2024
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	<StructureSection load='6qbh' size='340' side='right'caption='[[6qbh]], [[Resolution\|resolution]] 1.85Å' scene=''>		<StructureSection load='6qbh' size='340' side='right'caption='[[6qbh]], [[Resolution\|resolution]] 1.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qbh]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QBH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QBH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qbh]] 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=6QBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QBH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=S43:(4~{S},5~{S},9~{S})-5-oxidanyl-4-(phenylmethyl)-9-propan-2-yl-1-oxa-3,8,11-triazacyclodocosane-2,7,10-trione'>S43</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]] 1.85Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qbg\|6qbg]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=S43:(4~{S},5~{S},9~{S})-5-oxidanyl-4-(phenylmethyl)-9-propan-2-yl-1-oxa-3,8,11-triazacyclodocosane-2,7,10-trione'>S43</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_D Cathepsin D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.5 3.4.23.5] </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=6qbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qbh OCA], [https://pdbe.org/6qbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qbh RCSB], [https://www.ebi.ac.uk/pdbsum/6qbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qbh 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=6qbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qbh OCA], [~~http~~://pdbe.org/6qbh PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qbh RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qbh PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qbh ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[~~http~~://omim.org/entry/610127 610127]]; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.<ref>PMID:16670177</ref> <ref>PMID:16685649</ref> <ref>PMID:21990111</ref>	+	[https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[https://omim.org/entry/610127 610127]; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.<ref>PMID:16670177</ref> <ref>PMID:16685649</ref> <ref>PMID:21990111</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.	+	[https://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6qbh" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qbh" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Cathepsin 3D structures\|Cathepsin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Cathepsin D]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Brynda, J]]	+	[[Category: Brynda J]]
-	[[Category: Houstecka, R]]	+	[[Category: Houstecka R]]
-	[[Category: Majer, P]]	+	[[Category: Majer P]]
-	[[Category: Mares, M]]	+	[[Category: Mares M]]
-	~~[[Category: Aspartic protease]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Peptidomimetic inhibitor~~]]	+

OCA at 07:28, 19 February 2020

OCA — Wed, 19 Feb 2020 07:28:40 GMT

←Older revision		Revision as of 07:28, 19 February 2020
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.		[[http://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human cathepsin D (CatD), a pepsin-family aspartic protease, plays an important role in tumor progression and metastasis. Here, we report the development of biomimetic inhibitors of CatD as novel tools for regulation of this therapeutic target. We designed a macrocyclic scaffold to mimic the spatial conformation of the minimal pseudo-dipeptide binding motif of pepstatin A, a microbial oligopeptide inhibitor, in the CatD active site. A library of more than 30 macrocyclic peptidomimetic inhibitors was employed for scaffold optimization, mapping of subsite interactions, and profiling of inhibitor selectivity. Furthermore, we solved high-resolution crystal structures of three macrocyclic inhibitors with low nanomolar or subnanomolar potency in complex with CatD and determined their binding mode using quantum chemical calculations. The study provides a new structural template and functional profile that can be exploited for design of potential chemotherapeutics that specifically inhibit CatD and related aspartic proteases.
		+
		+	Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure-Activity Relationship and Binding Mode Analysis.,Houstecka R, Hadzima M, Fanfrlik J, Brynda J, Pallova L, Hanova I, Mertlikova-Kaiserova H, Lepsik M, Horn M, Smrcina M, Majer P, Mares M J Med Chem. 2020 Feb 13. doi: 10.1021/acs.jmedchem.9b01351. PMID:32003991<ref>PMID:32003991</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qbh" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:34, 29 January 2020

OCA — Wed, 29 Jan 2020 15:34:12 GMT

←Older revision		Revision as of 15:34, 29 January 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qbh is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 33==
-		+	<StructureSection load='6qbh' size='340' side='right'caption='[[6qbh]], [[Resolution\|resolution]] 1.85Å' scene=''>
-	~~Authors~~: ~~Brynda~~, J., ~~Houstecka~~, R., ~~Majer~~, P., ~~Mares, M~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qbh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QBH FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~human~~ cathepsin D ~~in complex~~ with ~~macrocyclic inhibitor 33~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=S43:(4~{S},5~{S},9~{S})-5-oxidanyl-4-(phenylmethyl)-9-propan-2-yl-1-oxa-3,8,11-triazacyclodocosane-2,7,10-trione'>S43</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qbg\|6qbg]]</td></tr>
-	[[Category: ~~Mares, M~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_D Cathepsin D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.5 3.4.23.5] </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=6qbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qbh OCA], [http://pdbe.org/6qbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qbh RCSB], [http://www.ebi.ac.uk/pdbsum/6qbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qbh ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:[http://omim.org/entry/610127 610127]]; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.<ref>PMID:16670177</ref> <ref>PMID:16685649</ref> <ref>PMID:21990111</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CATD_HUMAN CATD_HUMAN]] Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cathepsin D]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Brynda, J]]		[[Category: Brynda, J]]
	[[Category: Houstecka, R]]		[[Category: Houstecka, R]]
	[[Category: Majer, P]]		[[Category: Majer, P]]
		+	[[Category: Mares, M]]
		+	[[Category: Aspartic protease]]
		+	[[Category: Hydrolase]]
		+	[[Category: Peptidomimetic inhibitor]]

OCA at 04:37, 24 July 2019

OCA — Wed, 24 Jul 2019 04:37:43 GMT

←Older revision		Revision as of 04:37, 24 July 2019
Line 5:		Line 5:
	Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M.		Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M.

-	Description: Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 37	+	Description: Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 33
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Mares, M]]		[[Category: Mares, M]]

OCA at 05:08, 9 January 2019

OCA — Wed, 09 Jan 2019 05:08:34 GMT

←Older revision		Revision as of 05:08, 9 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6qbh is ON HOLD	+	The entry 6qbh is ON HOLD until Paper Publication

	Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M.		Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M.

OCA: Protected "6qbh" [edit=sysop:move=sysop]

OCA — Wed, 26 Dec 2018 07:05:45 GMT

Protected "6qbh" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:05, 26 December 2018

OCA: New page: '''Unreleased structure''' The entry 6qbh is ON HOLD Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M. Description: Crystal structure of human cathepsin D in complex with macroc...

OCA — Wed, 26 Dec 2018 07:05:44 GMT

New page: '''Unreleased structure''' The entry 6qbh is ON HOLD Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M. Description: Crystal structure of human cathepsin D in complex with macroc...

New page

'''Unreleased structure'''

The entry 6qbh is ON HOLD

Authors: Brynda, J., Houstecka, R., Majer, P., Mares, M.

Description: Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 37
[[Category: Unreleased Structures]]
[[Category: Mares, M]]
[[Category: Brynda, J]]
[[Category: Houstecka, R]]
[[Category: Majer, P]]