8ohv: Difference between revisions

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-'''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]] 1.50&Aring;' 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]] 1.5&#8491;</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&reg;/PubMed&reg;, 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]]