5kx9: Difference between revisions
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==Selective Small Molecule Inhibition of the FMN Riboswitch== | ==Selective Small Molecule Inhibition of the FMN Riboswitch== | ||
<StructureSection load='5kx9' size='340' side='right' caption='[[5kx9]], [[Resolution|resolution]] 2.90Å' scene=''> | <StructureSection load='5kx9' size='340' side='right'caption='[[5kx9]], [[Resolution|resolution]] 2.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5kx9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KX9 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5kx9]] 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=5KX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KX9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YG:2-[(3~{S})-1-[(2-METHOXYPYRIMIDIN-5-YL)METHYL]PIPERIDIN-3-YL]-6-THIOPHEN-2-YL-1~{H}-PYRIMIDIN-4-ONE'>6YG</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6YG:2-[(3~{S})-1-[(2-METHOXYPYRIMIDIN-5-YL)METHYL]PIPERIDIN-3-YL]-6-THIOPHEN-2-YL-1~{H}-PYRIMIDIN-4-ONE'>6YG</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=5kx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kx9 OCA], [https://pdbe.org/5kx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kx9 RCSB], [https://www.ebi.ac.uk/pdbsum/5kx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kx9 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5kx9" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5kx9" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Riboswitch 3D structures|Riboswitch 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Fusobacterium nucleatum]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Fischmann TO]] | ||
Latest revision as of 12:14, 25 October 2023
Selective Small Molecule Inhibition of the FMN RiboswitchSelective Small Molecule Inhibition of the FMN Riboswitch
Structural highlights
Publication Abstract from PubMedBacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil is structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs. Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch.,Howe JA, Xiao L, Fischmann TO, Wang H, Tang H, Villafania A, Zhang R, Barbieri CM, Roemer T RNA Biol. 2016 Aug 2:1-9. PMID:27485612[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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