View source for 8ohu


==Crystal structure of Beta-glucuronidase from Acidobacterium capsulatum in complex with glucuronic acid configured isofagamine==
<StructureSection load='8ohu' size='340' side='right'caption='[[8ohu]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ohu]] 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=8OHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OHU 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]] 1.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SJ5:(3S,4R,5R)-4,5-dihydroxypiperidine-3-carboxylic+acid'>SJ5</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=8ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ohu OCA], [https://pdbe.org/8ohu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ohu RCSB], [https://www.ebi.ac.uk/pdbsum/8ohu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ohu 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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ohu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acidobacterium capsulatum]]
[[Category: Large Structures]]
[[Category: Armstrong Z]]
[[Category: Davies GJ]]
[[Category: Overkleeft HS]]
[[Category: Wu L]]
[[Category: Yurong C]]