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==Crystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amine== | ==Crystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amine== | ||
<StructureSection load='4nyc' size='340' side='right' caption='[[4nyc]], [[Resolution|resolution]] 3.15Å' scene=''> | <StructureSection load='4nyc' size='340' side='right' caption='[[4nyc]], [[Resolution|resolution]] 3.15Å' scene=''> | ||
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A23:ADENOSINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>A23</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A23:ADENOSINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>A23</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nya|4nya]], [[4nyb|4nyb]], [[4nyd|4nyd]], [[4nyg|4nyg]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nya|4nya]], [[4nyb|4nyb]], [[4nyd|4nyd]], [[4nyg|4nyg]]</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=4nyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nyc RCSB], [http://www.ebi.ac.uk/pdbsum/4nyc PDBsum]</span></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=4nyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyc OCA], [http://pdbe.org/4nyc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nyc RCSB], [http://www.ebi.ac.uk/pdbsum/4nyc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4nyc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Riboswitch|Riboswitch]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 19:04, 11 August 2016
Crystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amineCrystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amine
Structural highlights
Publication Abstract from PubMedThiamine pyrophosphate (TPP) riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Previous studies using fragment-based approaches identified small molecule "fragments" that bind this gene-regulatory mRNA domain. Crystallographic studies now show that, despite having micromolar Kds, four different fragments bind the TPP riboswitch site-specifically, occupying the pocket that recognizes the aminopyrimidine of TPP. Unexpectedly, the unoccupied site that would recognize the pyrophosphate of TPP rearranges into a structure distinct from that of the cognate complex. This idiosyncratic fragment-induced conformation, also characterized by small-angle X-ray scattering and chemical probing, represents a possible mechanism for adventitious ligand discrimination by the riboswitch, and suggests that off-pathway conformations of RNAs can be targeted for drug development. Our structures, together with previous screening studies, demonstrate the feasibility of fragment-based drug discovery against RNA targets. Validating Fragment-Based Drug Discovery for Biological RNAs: Lead Fragments Bind and Remodel the TPP Riboswitch Specifically.,Warner KD, Homan P, Weeks KM, Smith AG, Abell C, Ferre-D'Amare AR Chem Biol. 2014 May 22;21(5):591-5. doi: 10.1016/j.chembiol.2014.03.007. Epub, 2014 Apr 24. PMID:24768306[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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