6wzr: Difference between revisions
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==Fusibacterium ulcerans ZTP riboswitch bound to p-1-pyridinyl AICA== | ==Fusibacterium ulcerans ZTP riboswitch bound to p-1-pyridinyl AICA== | ||
<StructureSection load='6wzr' size='340' side='right'caption='[[6wzr]]' scene=''> | <StructureSection load='6wzr' size='340' side='right'caption='[[6wzr]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WZR FirstGlance]. <br> | <table><tr><td colspan='2'>[[6wzr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Fusobacterium_ulcerans Fusobacterium ulcerans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WZR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WZR FirstGlance]. <br> | ||
</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=6wzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wzr OCA], [https://pdbe.org/6wzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wzr RCSB], [https://www.ebi.ac.uk/pdbsum/6wzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wzr ProSAT]</span></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]] 3.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=UG1:5-amino-1-(pyridin-4-yl)-1H-imidazole-4-carboxamide'>UG1</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=6wzr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wzr OCA], [https://pdbe.org/6wzr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wzr RCSB], [https://www.ebi.ac.uk/pdbsum/6wzr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wzr ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Riboswitches are mRNA domains that make gene-regulatory decisions upon binding their cognate ligands. Bacterial riboswitches that specifically recognize 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP) and 5'-triphosphate (ZTP) regulate genes involved in folate and purine metabolism. Now, we have developed synthetic ligands targeting ZTP riboswitches by replacing the sugar-phosphate moiety of ZMP with various functional groups, including simple heterocycles. Despite losing hydrogen bonds from ZMP, these analogs bind ZTP riboswitches with similar affinities as the natural ligand, and activate transcription more strongly than ZMP in vitro. The most active ligand stimulates gene expression approximately 3 times more than ZMP in a live Escherichia coli reporter. Co-crystal structures of the Fusobacterium ulcerans ZTP riboswitch bound to synthetic ligands suggest stacking of their pyridine moieties on a conserved RNA nucleobase primarily determines their higher activity. Altogether, these findings guide future design of improved riboswitch activators and yield insights into how RNA-targeted ligand discovery may proceed. | |||
Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design.,Tran B, Pichling P, Tenney L, Connelly CM, Moon MH, Ferre-D'Amare AR, Schneekloth JS Jr, Jones CP Cell Chem Biol. 2020 Oct 15;27(10):1241-1249.e4. doi:, 10.1016/j.chembiol.2020.07.021. Epub 2020 Aug 13. PMID:32795418<ref>PMID:32795418</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6wzr" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Riboswitch 3D structures|Riboswitch 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Fusobacterium ulcerans]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ferre-D'Amare AR]] | [[Category: Ferre-D'Amare AR]] | ||
Latest revision as of 17:39, 18 October 2023
Fusibacterium ulcerans ZTP riboswitch bound to p-1-pyridinyl AICAFusibacterium ulcerans ZTP riboswitch bound to p-1-pyridinyl AICA
Structural highlights
Publication Abstract from PubMedRiboswitches are mRNA domains that make gene-regulatory decisions upon binding their cognate ligands. Bacterial riboswitches that specifically recognize 5-aminoimidazole-4-carboxamide riboside 5'-monophosphate (ZMP) and 5'-triphosphate (ZTP) regulate genes involved in folate and purine metabolism. Now, we have developed synthetic ligands targeting ZTP riboswitches by replacing the sugar-phosphate moiety of ZMP with various functional groups, including simple heterocycles. Despite losing hydrogen bonds from ZMP, these analogs bind ZTP riboswitches with similar affinities as the natural ligand, and activate transcription more strongly than ZMP in vitro. The most active ligand stimulates gene expression approximately 3 times more than ZMP in a live Escherichia coli reporter. Co-crystal structures of the Fusobacterium ulcerans ZTP riboswitch bound to synthetic ligands suggest stacking of their pyridine moieties on a conserved RNA nucleobase primarily determines their higher activity. Altogether, these findings guide future design of improved riboswitch activators and yield insights into how RNA-targeted ligand discovery may proceed. Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design.,Tran B, Pichling P, Tenney L, Connelly CM, Moon MH, Ferre-D'Amare AR, Schneekloth JS Jr, Jones CP Cell Chem Biol. 2020 Oct 15;27(10):1241-1249.e4. doi:, 10.1016/j.chembiol.2020.07.021. Epub 2020 Aug 13. PMID:32795418[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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