View source for 7psh


==Crystal structure of beta-glucuronidase from Acidobacterium capsulatum at 1.24 Angstrom resolution==
<StructureSection load='7psh' size='340' side='right'caption='[[7psh]], [[Resolution|resolution]] 1.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7psh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Acidobacterium_capsulatum_ATCC_51196 Acidobacterium capsulatum ATCC 51196]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PSH 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]] 1.24&#8491;</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=7psh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7psh OCA], [https://pdbe.org/7psh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7psh RCSB], [https://www.ebi.ac.uk/pdbsum/7psh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7psh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C1F2K5_ACIC5 C1F2K5_ACIC5] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Heparan sulfate proteoglycans (HSPGs) mediate essential interactions throughout the extracellular matrix (ECM), providing signals that regulate cellular growth and development. Altered HSPG composition during tumorigenesis strongly aids cancer progression. Heparanase (HPSE) is the principal enzyme responsible for extracellular heparan sulfate catabolism and is markedly up-regulated in aggressive cancers. HPSE overactivity degrades HSPGs within the ECM, facilitating metastatic dissemination and releasing mitogens that drive cellular proliferation. Reducing extracellular HPSE activity reduces cancer growth, but few effective inhibitors are known, and none are clinically approved. Inspired by the natural glycosidase inhibitor cyclophellitol, we developed nanomolar mechanism-based, irreversible HPSE inhibitors that are effective within physiological environments. Application of cyclophellitol-derived HPSE inhibitors reduces cancer aggression in cellulo and significantly ameliorates murine metastasis. Mechanism-based irreversible HPSE inhibition is an unexplored anticancer strategy. We demonstrate the feasibility of such compounds to control pathological HPSE-driven malignancies.

Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo.,de Boer C, Armstrong Z, Lit VAJ, Barash U, Ruijgrok G, Boyango I, Weitzenberg MM, Schroder SP, Sarris AJC, Meeuwenoord NJ, Bule P, Kayal Y, Ilan N, Codee JDC, Vlodavsky I, Overkleeft HS, Davies GJ, Wu L Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2203167119. doi:, 10.1073/pnas.2203167119. Epub 2022 Jul 26. PMID:35881786<ref>PMID:35881786</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7psh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acidobacterium capsulatum ATCC 51196]]
[[Category: Large Structures]]
[[Category: Armstrong Z]]
[[Category: Davies GJ]]
[[Category: Wu L]]