6uc9: Difference between revisions
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==Guanine riboswitch bound to O6-cyclohexylmethyl guanine== | ==Guanine riboswitch bound to O6-cyclohexylmethyl guanine== | ||
<StructureSection load='6uc9' size='340' side='right'caption='[[6uc9]]' scene=''> | <StructureSection load='6uc9' size='340' side='right'caption='[[6uc9]], [[Resolution|resolution]] 1.94Å' 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=6UC9 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6uc9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UC9 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.941Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CMG:6-O-CYCLOHEXYLMETHYL+GUANINE'>CMG</scene>, <scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</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=6uc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uc9 OCA], [https://pdbe.org/6uc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uc9 RCSB], [https://www.ebi.ac.uk/pdbsum/6uc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uc9 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Riboswitches are important model systems for the development of approaches to search for RNA-targeting therapeutics. A principal challenge in finding compounds that target riboswitches is that the effector ligand is typically almost completely encapsulated by the RNA, which severely limits the chemical space that can be explored. Efforts to find compounds that bind the guanine/adenine class of riboswitches with a high affinity have in part focused on purines modified at the C6 and C2 positions. These studies have revealed compounds that have low to sub-micromolar affinity and, in a few cases, have antimicrobial activity. To further understand how these compounds interact with the guanine riboswitch, we have performed an integrated structural and functional analysis of representative guanine derivatives with modifications at the C8, C6 and C2 positions. Our data indicate that while modifications of guanine at the C6 position are generally unfavorable, modifications at the C8 and C2 positions yield compounds that rival guanine with respect to binding affinity. Surprisingly, C2-modified guanines such as N2-acetylguanine completely disrupt a key Watson-Crick pairing interaction between the ligand and RNA. These compounds, which also modulate transcriptional termination as efficiently as guanine, open up a significant new chemical space of guanine modifications in the search for antimicrobial agents that target purine riboswitches. | |||
High Affinity Binding of N2-Modified Guanine Derivatives Significantly Disrupts the Ligand Binding Pocket of the Guanine Riboswitch.,Matyjasik MM, Hall SD, Batey RT Molecules. 2020 May 13;25(10). pii: molecules25102295. doi:, 10.3390/molecules25102295. PMID:32414072<ref>PMID:32414072</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6uc9" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Riboswitch 3D structures|Riboswitch 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacillus subtilis]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Batey RT]] | [[Category: Batey RT]] | ||
[[Category: Matyjasik MM]] | [[Category: Matyjasik MM]] | ||
Latest revision as of 10:49, 11 October 2023
Guanine riboswitch bound to O6-cyclohexylmethyl guanineGuanine riboswitch bound to O6-cyclohexylmethyl guanine
Structural highlights
Publication Abstract from PubMedRiboswitches are important model systems for the development of approaches to search for RNA-targeting therapeutics. A principal challenge in finding compounds that target riboswitches is that the effector ligand is typically almost completely encapsulated by the RNA, which severely limits the chemical space that can be explored. Efforts to find compounds that bind the guanine/adenine class of riboswitches with a high affinity have in part focused on purines modified at the C6 and C2 positions. These studies have revealed compounds that have low to sub-micromolar affinity and, in a few cases, have antimicrobial activity. To further understand how these compounds interact with the guanine riboswitch, we have performed an integrated structural and functional analysis of representative guanine derivatives with modifications at the C8, C6 and C2 positions. Our data indicate that while modifications of guanine at the C6 position are generally unfavorable, modifications at the C8 and C2 positions yield compounds that rival guanine with respect to binding affinity. Surprisingly, C2-modified guanines such as N2-acetylguanine completely disrupt a key Watson-Crick pairing interaction between the ligand and RNA. These compounds, which also modulate transcriptional termination as efficiently as guanine, open up a significant new chemical space of guanine modifications in the search for antimicrobial agents that target purine riboswitches. High Affinity Binding of N2-Modified Guanine Derivatives Significantly Disrupts the Ligand Binding Pocket of the Guanine Riboswitch.,Matyjasik MM, Hall SD, Batey RT Molecules. 2020 May 13;25(10). pii: molecules25102295. doi:, 10.3390/molecules25102295. PMID:32414072[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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