5kx9: Difference between revisions
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The | ==Selective Small Molecule Inhibition of the FMN Riboswitch== | ||
<StructureSection load='5kx9' size='340' side='right' caption='[[5kx9]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== 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 [http://oca.weizmann.ac.il/oca-docs/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> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kx9 OCA], [http://pdbe.org/5kx9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kx9 RCSB], [http://www.ebi.ac.uk/pdbsum/5kx9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kx9 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bacterial 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<ref>PMID:27485612</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5kx9" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Fischmann, T O]] | |||
[[Category: Rna]] | |||
[[Category: Rna-inhibitor complex]] | |||
[[Category: Translation]] | |||
Revision as of 09:54, 10 September 2016
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. References
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