OCA at 10:25, 10 January 2024

OCA — Wed, 10 Jan 2024 10:25:35 GMT

←Older revision		Revision as of 10:25, 10 January 2024
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8ohv is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Beta-glucuronidase from Acidobacterium capsulatum in complex with glucuronic acid configured 3-geminal diol iminosugar inhibitor==
		+	<StructureSection load='8ohv' size='340' side='right'caption='[[8ohv]], [[Resolution\|resolution]] 1.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8ohv]] 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=8OHV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OHV FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VP5:(3~{S},4~{R})-4,5,5-tris(oxidanyl)piperidine-3-carboxylic+acid'>VP5</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=8ohv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ohv OCA], [https://pdbe.org/8ohv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ohv RCSB], [https://www.ebi.ac.uk/pdbsum/8ohv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ohv ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/C1F2K5_ACIC5 C1F2K5_ACIC5]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Siastatin B is a potent and effective iminosugar inhibitor of three diverse glycosidase classes, namely, sialidases, beta-d-glucuronidases, and N-acetyl-glucosaminidases. The mode of inhibition of glucuronidases, in contrast to sialidases, has long been enigmatic as siastatin B appears too bulky and incorrectly substituted to be accommodated within a beta-d-glucuronidase active site pocket. Herein, we show through crystallographic analysis of protein-inhibitor complexes that siastatin B generates both a hemiaminal and a 3-geminal diol iminosugar (3-GDI) that are, rather than the parent compound, directly responsible for enzyme inhibition. The hemiaminal product is the first observation of a natural product that belongs to the noeuromycin class of inhibitors. Additionally, the 3-GDI represents a new and potent class of the iminosugar glycosidase inhibitor. To substantiate our findings, we synthesized both the gluco- and galacto-configured 3-GDIs and characterized their binding both structurally and kinetically to exo-beta-d-glucuronidases and the anticancer target human heparanase. This revealed submicromolar inhibition of exo-beta-d-glucuronidases and an unprecedented binding mode by this new class of inhibitor. Our results reveal the mechanism by which siastatin B acts as a broad-spectrum glycosidase inhibitor, identify a new class of glycosidase inhibitor, and suggest new functionalities that can be incorporated into future generations of glycosidase inhibitors.

-	~~Authors: Armstrong, Z~~., ~~Yurong~~, C., Wu, L., ~~Overkleeft~~, ~~H.S.~~, Davies, G.J.	+	Molecular Basis for Inhibition of Heparanases and beta-Glucuronidases by Siastatin B.,Chen Y, van den Nieuwendijk AMCH, Wu L, Moran E, Skoulikopoulou F, van Riet V, Overkleeft HS, Davies GJ, Armstrong Z J Am Chem Soc. 2023 Dec 20. doi: 10.1021/jacs.3c04162. PMID:38118176<ref>PMID:38118176</ref>

-	~~Description: Crystal structure~~ of ~~Beta~~-~~glucuronidase from~~ Acidobacterium capsulatum ~~in complex with glucuronic acid configured 3-geminal diol iminosugar inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Yurong, C~~]]	+	<div class="pdbe-citations 8ohv" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Overkleeft, H.S~~]]	+	== References ==
-	[[Category: ~~Wu, L~~]]	+	<references/>
-	[[Category: ~~Davies, G.J~~]]	+	__TOC__
-	[[Category: ~~Armstrong, Z~~]]	+	</StructureSection>
		+	[[Category: Acidobacterium capsulatum]]
		+	[[Category: Large Structures]]
		+	[[Category: Armstrong Z]]
		+	[[Category: Davies GJ]]
		+	[[Category: Overkleeft HS]]
		+	[[Category: Wu L]]
		+	[[Category: Yurong C]]

OCA at 15:11, 26 April 2023

OCA — Wed, 26 Apr 2023 15:11:57 GMT

←Older revision		Revision as of 15:11, 26 April 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Armstrong, Z., Yurong, C., Wu, L., Overkleeft, H.S., Davies, G.J.		Authors: Armstrong, Z., Yurong, C., Wu, L., Overkleeft, H.S., Davies, G.J.

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

OCA — Wed, 29 Mar 2023 05:08:03 GMT

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

←Older revision

Revision as of 05:08, 29 March 2023

OCA: New page: '''Unreleased structure''' The entry 8ohv is ON HOLD Authors: Armstrong, Z., Yurong, C., Wu, L., Overkleeft, H.S., Davies, G.J. Description: Crystal structure of Beta-glucuronidase fro...

OCA — Wed, 29 Mar 2023 05:07:59 GMT

New page: '''Unreleased structure''' The entry 8ohv is ON HOLD Authors: Armstrong, Z., Yurong, C., Wu, L., Overkleeft, H.S., Davies, G.J. Description: Crystal structure of Beta-glucuronidase fro...

New page

'''Unreleased structure'''

The entry 8ohv is ON HOLD

Authors: Armstrong, Z., Yurong, C., Wu, L., Overkleeft, H.S., Davies, G.J.

Description: Crystal structure of Beta-glucuronidase from Acidobacterium capsulatum in complex with glucuronic acid configured 3-geminal diol iminosugar inhibitor
[[Category: Unreleased Structures]]
[[Category: Yurong, C]]
[[Category: Overkleeft, H.S]]
[[Category: Wu, L]]
[[Category: Davies, G.J]]
[[Category: Armstrong, Z]]

8ohv - Revision history

OCA at 10:25, 10 January 2024

OCA at 15:11, 26 April 2023

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

OCA: New page: '''Unreleased structure''' The entry 8ohv is ON HOLD Authors: Armstrong, Z., Yurong, C., Wu, L., Overkleeft, H.S., Davies, G.J. Description: Crystal structure of Beta-glucuronidase fro...