8b0e - Revision history

OCA at 08:15, 7 February 2024

OCA — Wed, 07 Feb 2024 08:15:28 GMT

←Older revision		Revision as of 08:15, 7 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8b0e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acidobacterium_capsulatum Acidobacterium capsulatum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B0E FirstGlance]. <br>		<table><tr><td colspan='2'>[[8b0e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acidobacterium_capsulatum Acidobacterium capsulatum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B0E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OV3:(1~{S},2~{R},3~{R},4~{S},6~{S})-3,4,6-tris(oxidanyl)-2-[2-[2,2,2-tris(fluoranyl)ethanoylamino]ethoxy]cyclohexane-1-carboxylic+acid'>OV3</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]] 1.55Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OV3:(1~{S},2~{R},3~{R},4~{S},6~{S})-3,4,6-tris(oxidanyl)-2-[2-[2,2,2-tris(fluoranyl)ethanoylamino]ethoxy]cyclohexane-1-carboxylic+acid'>OV3</scene></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=8b0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b0e OCA], [https://pdbe.org/8b0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b0e RCSB], [https://www.ebi.ac.uk/pdbsum/8b0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b0e 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=8b0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b0e OCA], [https://pdbe.org/8b0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b0e RCSB], [https://www.ebi.ac.uk/pdbsum/8b0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b0e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/C1F2K5_ACIC5 C1F2K5_ACIC5]		[https://www.uniprot.org/uniprot/C1F2K5_ACIC5 C1F2K5_ACIC5]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Degradation of the extracellular matrix (ECM) supports tissue integrity and homeostasis, but is also a key factor in cancer metastasis. Heparanase (HPSE) is a mammalian ECM-remodeling enzyme with beta-D-endo-glucuronidase activity overexpressed in several malignancies, and is thought to facilitate tumor growth and metastasis. By this virtue, HPSE is considered an attractive target for the development of cancer therapies, yet to date no HPSE inhibitors have progressed to the clinic. Here we report on the discovery of glucurono-configured cyclitol derivatives featuring simple substituents at the 4-O-position as irreversible HPSE inhibitors. We show that these compounds, unlike glucurono-cyclophellitol, are selective for HPSE over beta-D-exo-glucuronidase (GUSB), also in platelet lysate. The observed selectivity is induced by steric and electrostatic interactions of the substituents at the 4-O-position. Crystallographic analysis supports this rationale for HPSE selectivity, and computer simulations provide insights in the conformational preferences and binding poses of the inhibitors, which we believe are good starting points for the future development of HPSE-targeting antimetastatic cancer drugs.
-
-	4-O-Substituted Glucuronic Cyclophellitols are Selective Mechanism-Based Heparanase Inhibitors.,Borlandelli V, Armstrong Z, Nin-Hill A, Codee J, Raich L, Artola M, Rovira C, Davies G, Overkleeft HS ChemMedChem. 2022 Dec 19. doi: 10.1002/cmdc.202200580. PMID:36533564<ref>PMID:36533564</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 8b0e" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 09:04, 28 December 2022

OCA — Wed, 28 Dec 2022 09:04:28 GMT

←Older revision		Revision as of 09:04, 28 December 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8b0e is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of beta-glucuronidase from Acidobacterium capsulatum in complex with covalent inhibitor VB158==
		+	<StructureSection load='8b0e' size='340' side='right'caption='[[8b0e]], [[Resolution\|resolution]] 1.55Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8b0e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acidobacterium_capsulatum Acidobacterium capsulatum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B0E FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OV3:(1~{S},2~{R},3~{R},4~{S},6~{S})-3,4,6-tris(oxidanyl)-2-[2-[2,2,2-tris(fluoranyl)ethanoylamino]ethoxy]cyclohexane-1-carboxylic+acid'>OV3</scene></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=8b0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b0e OCA], [https://pdbe.org/8b0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b0e RCSB], [https://www.ebi.ac.uk/pdbsum/8b0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b0e ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/C1F2K5_ACIC5 C1F2K5_ACIC5]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Degradation of the extracellular matrix (ECM) supports tissue integrity and homeostasis, but is also a key factor in cancer metastasis. Heparanase (HPSE) is a mammalian ECM-remodeling enzyme with beta-D-endo-glucuronidase activity overexpressed in several malignancies, and is thought to facilitate tumor growth and metastasis. By this virtue, HPSE is considered an attractive target for the development of cancer therapies, yet to date no HPSE inhibitors have progressed to the clinic. Here we report on the discovery of glucurono-configured cyclitol derivatives featuring simple substituents at the 4-O-position as irreversible HPSE inhibitors. We show that these compounds, unlike glucurono-cyclophellitol, are selective for HPSE over beta-D-exo-glucuronidase (GUSB), also in platelet lysate. The observed selectivity is induced by steric and electrostatic interactions of the substituents at the 4-O-position. Crystallographic analysis supports this rationale for HPSE selectivity, and computer simulations provide insights in the conformational preferences and binding poses of the inhibitors, which we believe are good starting points for the future development of HPSE-targeting antimetastatic cancer drugs.

-	~~Authors: Armstrong~~, Z., ~~Davies~~, G.J.	+	4-O-Substituted Glucuronic Cyclophellitols are Selective Mechanism-Based Heparanase Inhibitors.,Borlandelli V, Armstrong Z, Nin-Hill A, Codee J, Raich L, Artola M, Rovira C, Davies G, Overkleeft HS ChemMedChem. 2022 Dec 19. doi: 10.1002/cmdc.202200580. PMID:36533564<ref>PMID:36533564</ref>

-	~~Description: Crystal structure~~ of ~~beta~~-~~glucuronidase from~~ Acidobacterium capsulatum ~~in complex with covalent inhibitor VB158~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Davies, G.J~~]]	+	<div class="pdbe-citations 8b0e" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Armstrong, Z~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Acidobacterium capsulatum]]
		+	[[Category: Large Structures]]
		+	[[Category: Armstrong Z]]
		+	[[Category: Davies GJ]]

OCA at 03:47, 26 October 2022

OCA — Wed, 26 Oct 2022 03:47:44 GMT

←Older revision		Revision as of 03:47, 26 October 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8b0e is ON HOLD	+	The entry 8b0e is ON HOLD until Paper Publication

	Authors: Armstrong, Z., Davies, G.J.		Authors: Armstrong, Z., Davies, G.J.

OCA: Protected "8b0e" [edit=sysop:move=sysop]

OCA — Wed, 14 Sep 2022 05:41:50 GMT

Protected "8b0e" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:41, 14 September 2022

OCA: New page: '''Unreleased structure''' The entry 8b0e is ON HOLD Authors: Armstrong, Z., Davies, G.J. Description: Crystal structure of beta-glucuronidase from Acidobacterium capsulatum in complex...

OCA — Wed, 14 Sep 2022 05:41:49 GMT

New page: '''Unreleased structure''' The entry 8b0e is ON HOLD Authors: Armstrong, Z., Davies, G.J. Description: Crystal structure of beta-glucuronidase from Acidobacterium capsulatum in complex...

New page

'''Unreleased structure'''

The entry 8b0e is ON HOLD

Authors: Armstrong, Z., Davies, G.J.

Description: Crystal structure of beta-glucuronidase from Acidobacterium capsulatum in complex with covalent inhibitor VB158
[[Category: Unreleased Structures]]
[[Category: Davies, G.J]]
[[Category: Armstrong, Z]]