6qbg - Revision history

OCA at 11:57, 24 January 2024

2024-01-24T11:57:11Z

←Older revision		Revision as of 11:57, 24 January 2024
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	<StructureSection load='6qbg' size='340' side='right'caption='[[6qbg]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='6qbg' size='340' side='right'caption='[[6qbg]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qbg]] 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=6QBG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QBG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qbg]] 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=6QBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QBG 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=HVT:(3~{S},7~{S},8~{S})-8-(naphthalen-2-ylmethyl)-7-oxidanyl-3-propan-2-yl-1,4,9-triazacyclohenicosane-2,5,10-trione'>HVT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.8Å</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='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=HVT:(3~{S},7~{S},8~{S})-8-(naphthalen-2-ylmethyl)-7-oxidanyl-3-propan-2-yl-1,4,9-triazacyclohenicosane-2,5,10-trione'>HVT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6qbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qbg OCA], [~~http~~://pdbe.org/6qbg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qbg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qbg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qbg ProSAT]</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=6qbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qbg OCA], [https://pdbe.org/6qbg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qbg RCSB], [https://www.ebi.ac.uk/pdbsum/6qbg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qbg 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 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6qbg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qbg" 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

2020-02-19T07:28:38Z

←Older revision		Revision as of 07:28, 19 February 2020
Line 12:		Line 12:
	== 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 6qbg" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:34, 29 January 2020

2020-01-29T15:34:11Z

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

-	~~The entry~~ 6qbg is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 14==
-		+	<StructureSection load='6qbg' size='340' side='right'caption='[[6qbg]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	~~Authors~~: ~~Brynda~~, J., ~~Houstecka~~, R., ~~Majer~~, P., ~~Mares, M~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qbg]] 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=6QBG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QBG FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~human~~ cathepsin D ~~in complex~~ with ~~macrocyclic inhibitor 14~~	+	</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=HVT:(3~{S},7~{S},8~{S})-8-(naphthalen-2-ylmethyl)-7-oxidanyl-3-propan-2-yl-1,4,9-triazacyclohenicosane-2,5,10-trione'>HVT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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>
-	[[Category: ~~Mares, M~~]]	+	<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=6qbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qbg OCA], [http://pdbe.org/6qbg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qbg RCSB], [http://www.ebi.ac.uk/pdbsum/6qbg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qbg 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 05:08, 9 January 2019

2019-01-09T05:08:29Z

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

-	The entry 6qbg is ON HOLD	+	The entry 6qbg 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 "6qbg" [edit=sysop:move=sysop]

2018-12-26T07:05:37Z

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

←Older revision

Revision as of 07:05, 26 December 2018

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

2018-12-26T07:05:35Z

New page: '''Unreleased structure''' The entry 6qbg 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 6qbg is ON HOLD

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

Description: Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 14
[[Category: Unreleased Structures]]
[[Category: Mares, M]]
[[Category: Brynda, J]]
[[Category: Houstecka, R]]
[[Category: Majer, P]]