4nyc: Difference between revisions
New page: '''Unreleased structure''' The entry 4nyc is ON HOLD Authors: Warner, K.D., Homan, P., Weeks, K.M., Smith, A.G., Abell, C., Ferr -D'Amar , A.R. Description: Crystal structure of the E.... |
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==Crystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amine== | |||
<StructureSection load='4nyc' size='340' side='right'caption='[[4nyc]], [[Resolution|resolution]] 3.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4nyc]] 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=4NYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYC 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]] 3.15Å</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=SVN:THIENO[2,3-B]PYRAZIN-7-AMINE'>SVN</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=4nyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyc OCA], [https://pdbe.org/4nyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyc RCSB], [https://www.ebi.ac.uk/pdbsum/4nyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyc 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4nyc" 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]] | |||
Latest revision as of 20:04, 20 September 2023
Crystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amineCrystal structure of the E. coli thiM riboswitch in complex with thieno[2,3-b]pyrazin-7-amine
Structural highlights
Publication Abstract from PubMedThiamine 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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