View source for 4nyb


==Crystal structure of the E. coli thiM riboswitch in complex with (4-(1,2,3-thiadiazol-4-yl)phenyl)methanamine==
<StructureSection load='4nyb' size='340' side='right'caption='[[4nyb]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4nyb]] 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=4NYB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYB 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QC:1-[4-(1,2,3-THIADIAZOL-4-YL)PHENYL]METHANAMINE'>2QC</scene>, <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></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=4nyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyb OCA], [https://pdbe.org/4nyb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyb RCSB], [https://www.ebi.ac.uk/pdbsum/4nyb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyb ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Thiamine pyrophosphate (TPP) riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Previous studies using fragment-based approaches identified small molecule "fragments" that bind this gene-regulatory mRNA domain. Crystallographic studies now show that, despite having micromolar Kds, four different fragments bind the TPP riboswitch site-specifically, occupying the pocket that recognizes the aminopyrimidine of TPP. Unexpectedly, the unoccupied site that would recognize the pyrophosphate of TPP rearranges into a structure distinct from that of the cognate complex. This idiosyncratic fragment-induced conformation, also characterized by small-angle X-ray scattering and chemical probing, represents a possible mechanism for adventitious ligand discrimination by the riboswitch, and suggests that off-pathway conformations of RNAs can be targeted for drug development. Our structures, together with previous screening studies, demonstrate the feasibility of fragment-based drug discovery against RNA targets.

Validating Fragment-Based Drug Discovery for Biological RNAs: Lead Fragments Bind and Remodel the TPP Riboswitch Specifically.,Warner KD, Homan P, Weeks KM, Smith AG, Abell C, Ferre-D'Amare AR Chem Biol. 2014 May 22;21(5):591-5. doi: 10.1016/j.chembiol.2014.03.007. Epub, 2014 Apr 24. PMID:24768306<ref>PMID:24768306</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4nyb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Riboswitch 3D structures|Riboswitch 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Abell C]]
[[Category: Ferre-D'Amare AR]]
[[Category: Homan P]]
[[Category: Smith AG]]
[[Category: Warner KD]]
[[Category: Weeks KM]]