View source for 7tdc


==Crystal structure of the E. coli thiM riboswitch in complex with thiamine bisphosphonate, calcium ions==
<StructureSection load='7tdc' size='340' side='right'caption='[[7tdc]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7tdc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.46&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A23:ADENOSINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>A23</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GMI:[2-[3-[(4-azanyl-2-methyl-pyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-5-yl]ethoxy-oxidanyl-phosphoryl]methylphosphonic+acid'>GMI</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'>[https://proteopedia.org/fgij/fg.htm?mol=7tdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tdc OCA], [https://pdbe.org/7tdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tdc RCSB], [https://www.ebi.ac.uk/pdbsum/7tdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tdc ProSAT]</span></td></tr>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7tdc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Riboswitch 3D structures|Riboswitch 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Nuthanakanti A]]
[[Category: Serganov A]]