8cx8
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Stx2A1-BTB13086== | |
| + | <StructureSection load='8cx8' size='340' side='right'caption='[[8cx8]], [[Resolution|resolution]] 1.91Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8cx8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CX8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CX8 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]] 1.905Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=P1U:5-(4-chlorophenyl)furan-2-carboxylic+acid'>P1U</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8cx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cx8 OCA], [https://pdbe.org/8cx8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cx8 RCSB], [https://www.ebi.ac.uk/pdbsum/8cx8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cx8 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q8XBV2_ECOLX Q8XBV2_ECOLX] The A subunit is responsible for inhibiting protein synthesis through the catalytic inactivation of 60S ribosomal subunits. After endocytosis, the A subunit is cleaved by furin in two fragments, A1 and A2: A1 is the catalytically active fragment, and A2 is essential for holotoxin assembly with the B subunits.[ARBA:ARBA00043904] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Shiga toxins are the main virulence factors of Shiga toxin producing E. coli (STEC) and S. dysenteriae. There is no effective therapy to counter the disease caused by these toxins. The A1 subunits of Shiga toxins bind the C-termini of ribosomal P-stalk proteins to depurinate the sarcin/ricin loop. The ribosome binding site of Shiga toxin 2 has not been targeted by small molecules. We screened a fragment library against the A1 subunit of Shiga toxin 2 (Stx2A1) and identified a fragment, BTB13086, which bound at the ribosome binding site and mimicked the binding mode of the P-stalk proteins. We synthesized analogs of BTB13086 and identified a series of molecules with similar affinity and inhibitory activity. These are the first compounds that bind at the ribosome binding site of Stx2A1 and inhibit activity. These compounds hold great promise for further inhibitor development against STEC infection. | ||
| - | + | Fragment Screening to Identify Inhibitors Targeting Ribosome Binding of Shiga Toxin 2.,Rudolph MJ, Tsymbal AM, Dutta A, Davis SA, Algava B, Roberge JY, Tumer NE, Li XP ACS Infect Dis. 2024 Aug 9;10(8):2814-2825. doi: 10.1021/acsinfecdis.4c00224. , Epub 2024 Jun 14. PMID:38873918<ref>PMID:38873918</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Li | + | <div class="pdbe-citations 8cx8" style="background-color:#fffaf0;"></div> |
| - | [[Category: Rudolph | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Li XP]] | ||
| + | [[Category: Rudolph MJ]] | ||
Current revision
Stx2A1-BTB13086
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