4nya: Difference between revisions
No edit summary |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of the E. coli thiM riboswitch in complex with 5-(azidomethyl)-2-methylpyrimidin-4-amine== | ==Crystal structure of the E. coli thiM riboswitch in complex with 5-(azidomethyl)-2-methylpyrimidin-4-amine== | ||
<StructureSection load='4nya' size='340' side='right' caption='[[4nya]], [[Resolution|resolution]] 2.65Å' scene=''> | <StructureSection load='4nya' size='340' side='right'caption='[[4nya]], [[Resolution|resolution]] 2.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4nya]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NYA OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4nya]] is a 2 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=4NYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYA FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QB:5-(AZIDOMETHYL)-2-METHYLPYRIMIDIN-4-AMINE'>2QB</scene>, <scene name='pdbligand=CCC:CYTIDINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>CCC</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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=4nya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nya OCA], [https://pdbe.org/4nya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nya RCSB], [https://www.ebi.ac.uk/pdbsum/4nya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nya ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 20: | Line 19: | ||
==See Also== | ==See Also== | ||
*[[Riboswitch|Riboswitch]] | *[[Riboswitch 3D structures|Riboswitch 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Abell C]] | ||
[[Category: | [[Category: Ferre-D'Amare AR]] | ||
[[Category: Homan P]] | |||
[[Category: | [[Category: Smith AG]] | ||
[[Category: | [[Category: Warner KD]] | ||
[[Category: | [[Category: Weeks KM]] | ||
[[Category: | |||
Latest revision as of 20:04, 20 September 2023
Crystal structure of the E. coli thiM riboswitch in complex with 5-(azidomethyl)-2-methylpyrimidin-4-amineCrystal structure of the E. coli thiM riboswitch in complex with 5-(azidomethyl)-2-methylpyrimidin-4-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
|
| ||||||||||||||||||