3o8h: Difference between revisions
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==EthR from Mycobacterium tuberculosis in complex with compound BDM14950== | |||
<StructureSection load='3o8h' size='340' side='right' caption='[[3o8h]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3o8h]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O8H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O8H FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=O8H:4-IODO-N-[(1-{2-OXO-2-[4-(3-THIOPHEN-2-YL-1,2,4-OXADIAZOL-5-YL)PIPERIDIN-1-YL]ETHYL}-1H-1,2,3-TRIAZOL-4-YL)METHYL]BENZENESULFONAMIDE'>O8H</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u9n|1u9n]], [[3o8g|3o8g]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ethR, MT3970, Rv3855 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o8h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o8h RCSB], [http://www.ebi.ac.uk/pdbsum/3o8h PDBsum]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o8/3o8h_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In situ click chemistry has been successfully applied to probe the ligand binding domain of EthR, a mycobacterial transcriptional regulator known to control the sensitivity of Mycobacterium tuberculosis to several antibiotics. Specific protein-templated ligands were generated in situ from one azide and six clusters of 10 acetylenic fragments. Comparative X-ray structures of EthR complexed with either clicked ligand BDM14950 or its azide precursor showed ligand-dependent conformational impacts on the protein architecture. This approach revealed two mobile phenylalanine residues that control the access to a previously hidden hydrophobic pocket that can be further exploited for the development of structurally diverse EthR inhibitors. This report shows that protein-directed in situ chemistry allows medicinal chemists to explore the conformational space of a ligand-binding pocket and is thus a valuable tool to guide drug design in the complex path of hit-to-lead processes. | |||
Exploring Drug Target Flexibility Using in Situ Click Chemistry: Application to a Mycobacterial Transcriptional Regulator.,Willand N, Desroses M, Toto P, Dirie B, Lens Z, Villeret V, Rucktooa P, Locht C, Baulard A, Deprez B ACS Chem Biol. 2010 Aug 26. PMID:20704273<ref>PMID:20704273</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Baulard, A | [[Category: Baulard, A]] | ||
[[Category: Deprez, B | [[Category: Deprez, B]] | ||
[[Category: Desroses, M | [[Category: Desroses, M]] | ||
[[Category: Diri, B | [[Category: Diri, B]] | ||
[[Category: Lens, Z | [[Category: Lens, Z]] | ||
[[Category: Locht, C | [[Category: Locht, C]] | ||
[[Category: Rucktooa, P | [[Category: Rucktooa, P]] | ||
[[Category: Toto, P | [[Category: Toto, P]] | ||
[[Category: Villeret, V | [[Category: Villeret, V]] | ||
[[Category: Willand, N | [[Category: Willand, N]] | ||
[[Category: Dna]] | [[Category: Dna]] | ||
[[Category: Tetr-family]] | [[Category: Tetr-family]] | ||
[[Category: Transcription]] | [[Category: Transcription]] | ||
[[Category: Transcriptional regulatory repressor]] | [[Category: Transcriptional regulatory repressor]] | ||
Revision as of 07:15, 19 December 2014
EthR from Mycobacterium tuberculosis in complex with compound BDM14950
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