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New page: '''Unreleased structure''' The entry 6dn2 is ON HOLD Authors: Vicens, Q., Mondragon, E., Reyes, F.E., Berman, J., Kaur, H., Kells, K., Wickens, P., Wilson, J., Gadwood, R., Schostarez, ... |
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The | ==CRYSTAL STRUCTURE OF THE FMN RIBOSWITCH BOUND TO BRX1354 SPLIT RNA== | ||
<StructureSection load='6dn2' size='340' side='right'caption='[[6dn2]], [[Resolution|resolution]] 2.88Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6dn2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Fusobacterium_nucleatum Fusobacterium nucleatum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DN2 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]] 2.88Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GZG:4-{benzyl[2-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)ethyl]amino}butanoic+acid'>GZG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6dn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dn2 OCA], [https://pdbe.org/6dn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dn2 RCSB], [https://www.ebi.ac.uk/pdbsum/6dn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dn2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative -5FDQD- that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis and purification of derivatives; (3) in vitro testing for productive binding using two chemical probing methods; (4) in vitro transcription termination assays; (5) resolution of the crystal structures of the FMN riboswitch in complex with the most mature candidates. In the process, we delineated principles for productive binding to this riboswitch, thereby demonstrating the effectiveness of a coordinated structure-guided approach to designing drugs against RNA. | |||
Structure-activity relationship of flavin analogs that target the FMN riboswitch.,Vicens Q, Mondragon E, Reyes FE, Coish P, Aristoff P, Berman J, Kaur H, Kells KW, Wickens P, Wilson J, Gadwood RC, Schostarez HJ, Suto RK, Blount KF, Batey RT ACS Chem Biol. 2018 Aug 14. doi: 10.1021/acschembio.8b00533. PMID:30107111<ref>PMID:30107111</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6dn2" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Riboswitch 3D structures|Riboswitch 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Fusobacterium nucleatum]] | ||
[[Category: Schostarez | [[Category: Large Structures]] | ||
[[Category: | [[Category: Batey RT]] | ||
[[Category: | [[Category: Berman J]] | ||
[[Category: | [[Category: Blount KF]] | ||
[[Category: | [[Category: Coish P]] | ||
[[Category: Gadwood R]] | |||
[[Category: Kaur H]] | |||
[[Category: Kells K]] | |||
[[Category: Mondragon E]] | |||
[[Category: Reyes FE]] | |||
[[Category: Schostarez H]] | |||
[[Category: Suto RK]] | |||
[[Category: Vicens Q]] | |||
[[Category: Wickens P]] | |||
[[Category: Wilson J]] | |||
Latest revision as of 09:09, 11 October 2023
CRYSTAL STRUCTURE OF THE FMN RIBOSWITCH BOUND TO BRX1354 SPLIT RNACRYSTAL STRUCTURE OF THE FMN RIBOSWITCH BOUND TO BRX1354 SPLIT RNA
Structural highlights
Publication Abstract from PubMedThe flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative -5FDQD- that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis and purification of derivatives; (3) in vitro testing for productive binding using two chemical probing methods; (4) in vitro transcription termination assays; (5) resolution of the crystal structures of the FMN riboswitch in complex with the most mature candidates. In the process, we delineated principles for productive binding to this riboswitch, thereby demonstrating the effectiveness of a coordinated structure-guided approach to designing drugs against RNA. Structure-activity relationship of flavin analogs that target the FMN riboswitch.,Vicens Q, Mondragon E, Reyes FE, Coish P, Aristoff P, Berman J, Kaur H, Kells KW, Wickens P, Wilson J, Gadwood RC, Schostarez HJ, Suto RK, Blount KF, Batey RT ACS Chem Biol. 2018 Aug 14. doi: 10.1021/acschembio.8b00533. PMID:30107111[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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