7tda: Difference between revisions

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~~'''Unreleased structure'''~~

~~The entry~~ 7tda is ~~ON HOLD~~

==Crystal structure of the E. coli thiM riboswitch in complex with thiamine pyrophosphate, manganese ions==

== Structural highlights ==

<table><tr><td colspan='2'>[[7tda]] 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=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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</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=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='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>

== 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.

~~Authors~~:

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>

~~Description~~:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased~~ Structures]]

</div>

==See Also==

*[[Riboswitch 3D structures|Riboswitch 3D structures]]

== References ==

__TOC__

</StructureSection>

[[Category: Escherichia coli]]

[[Category: Large Structures]]

[[Category: Nuthanakanti A]]

[[Category: Serganov A]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7tda is ON HOLD
+==Crystal structure of the E. coli thiM riboswitch in complex with thiamine pyrophosphate, manganese ions==
+<StructureSection load='7tda' size='340' side='right'caption='[[7tda]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7tda]] 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=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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#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=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='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>
+<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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7tda" 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]]