7tda: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the E. coli thiM riboswitch in complex with thiamine pyrophosphate, manganese ions== | ==Crystal structure of the E. coli thiM riboswitch in complex with thiamine pyrophosphate, manganese ions== | ||
<StructureSection load='7tda' size='340' side='right'caption='[[7tda]]' scene=''> | <StructureSection load='7tda' size='340' side='right'caption='[[7tda]], [[Resolution|resolution]] 2.25Å' 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=7TDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDA FirstGlance]. <br> | <table><tr><td colspan='2'>[[7tda]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDA 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=7tda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tda OCA], [https://pdbe.org/7tda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tda RCSB], [https://www.ebi.ac.uk/pdbsum/7tda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tda ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7tda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tda OCA], [https://pdbe.org/7tda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tda RCSB], [https://www.ebi.ac.uk/pdbsum/7tda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tda ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
RNA molecules can show high levels of cooperativity in their global folding and interactions with divalent ions. However, cooperativity at individual ligand-RNA interaction sites remains poorly understood. Here, we investigated the binding of thiamine and methylene diphosphonic acid (MDP, a soluble structural analogue of pyrophosphate) to the thiamine pyrophosphate riboswitch. These ligands each bind weakly at proximal subsites, with 10 muM and 1 mM affinities, respectively. The affinity of MDP moderately improves when thiamine or thiamine-like fragments are pre-bound to the RNA. Covalent linking of thiamine and MDP substantially increases riboswitch binding to a notable high affinity of 20 nM. Crystal structures and single-molecule correlated chemical probing revealed favorable induced fit effects upon binding of individual ligands and, unexpectedly, a substantial thermodynamically unfavorable RNA structural rearrangement upon binding of the linked thiamine-MDP ligand. Thus, linking of two ligands of modest affinity, accompanied by an unfavorable structural rearrangement, still yields a potent linked RNA-binding compound. Since complex ligands often bind riboswitches and other RNAs at proximal subsites, principles derived from this work inform and support fragment-linking strategies for identifying small molecules that interact with RNA specifically and with high affinity. | |||
Subsite Ligand Recognition and Cooperativity in the TPP Riboswitch: Implications for Fragment-Linking in RNA Ligand Discovery.,Zeller MJ, Nuthanakanti A, Li K, Aube J, Serganov A, Weeks KM ACS Chem Biol. 2022 Jan 21. doi: 10.1021/acschembio.1c00880. PMID:35060698<ref>PMID:35060698</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7tda" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Nuthanakanti A]] | [[Category: Nuthanakanti, A]] | ||
[[Category: Serganov A]] | [[Category: Serganov, A]] | ||
[[Category: Rna]] | |||
Revision as of 07:32, 2 March 2022
Crystal structure of the E. coli thiM riboswitch in complex with thiamine pyrophosphate, manganese ions
| ||||||||||||
