7pr6
From Proteopedia
(Difference between revisions)
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==Crystal structure of E. coli beta-glucuronidase in complex with covalent inhibitor ME727== | ==Crystal structure of E. coli beta-glucuronidase in complex with covalent inhibitor ME727== | ||
| - | <StructureSection load='7pr6' size='340' side='right'caption='[[7pr6]]' scene=''> | + | <StructureSection load='7pr6' size='340' side='right'caption='[[7pr6]], [[Resolution|resolution]] 1.99Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PR6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7pr6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PR6 FirstGlance]. <br> |
| - | </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=7pr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pr6 OCA], [https://pdbe.org/7pr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pr6 RCSB], [https://www.ebi.ac.uk/pdbsum/7pr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pr6 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8I4:(2R,3S,5R,6R)-2,3,4,5,6-pentakis(oxidanyl)cyclohexane-1-carboxylic+acid'>8I4</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=7pr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pr6 OCA], [https://pdbe.org/7pr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pr6 RCSB], [https://www.ebi.ac.uk/pdbsum/7pr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pr6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/BGLR_ECOLI BGLR_ECOLI]] | ||
| + | <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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7pr6" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Escherichia coli K-12]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Armstrong Z]] | [[Category: Armstrong Z]] | ||
[[Category: Davies GJ]] | [[Category: Davies GJ]] | ||
[[Category: Wu L]] | [[Category: Wu L]] | ||
Revision as of 03:10, 8 September 2022
Crystal structure of E. coli beta-glucuronidase in complex with covalent inhibitor ME727
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