4nyb
From Proteopedia
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| - | ''' | + | ==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]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4nyb]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NYB FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QC:1-[4-(1,2,3-THIADIAZOL-4-YL)PHENYL]METHANAMINE'>2QC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A23:ADENOSINE-5-PHOSPHATE-2,3-CYCLIC+PHOSPHATE'>A23</scene></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nya|4nya]], [[4nyc|4nyc]], [[4nyd|4nyd]], [[4nyg|4nyg]]</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nyb RCSB], [http://www.ebi.ac.uk/pdbsum/4nyb PDBsum]</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> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Abell, C.]] | ||
| + | [[Category: Amare, A R.Ferre-D.]] | ||
| + | [[Category: Homan, P.]] | ||
| + | [[Category: Smith, A G.]] | ||
| + | [[Category: Warner, K D.]] | ||
| + | [[Category: Weeks, K M.]] | ||
| + | [[Category: Fragment-based drug discovery]] | ||
| + | [[Category: Riboswitch]] | ||
| + | [[Category: Rna]] | ||
Revision as of 05:05, 4 June 2014
Crystal structure of the E. coli thiM riboswitch in complex with (4-(1,2,3-thiadiazol-4-yl)phenyl)methanamine
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