5f27
From Proteopedia
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| - | ''' | + | ==Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound 2 at 1.68A resolution== |
| + | <StructureSection load='5f27' size='340' side='right' caption='[[5f27]], [[Resolution|resolution]] 1.68Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5f27]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F27 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5TT:~{N}-METHYL-1-(4-PIPERIDIN-1-YLPHENYL)METHANAMINE'>5TT</scene></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=5f27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f27 OCA], [http://pdbe.org/5f27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f27 RCSB], [http://www.ebi.ac.uk/pdbsum/5f27 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ETHR_MYCTO ETHR_MYCTO]] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | With the ever-increasing instances of resistance to frontline TB drugs there is the need to develop novel strategies to fight the worldwide TB epidemic. Boosting the effect of the existing second-line antibiotic ethionamide by inhibiting the mycobacterial transcriptional repressor protein EthR is an attractive therapeutic strategy. Herein we report the use of a fragment based drug discovery approach for the structure-guided systematic merging of two fragment molecules, each binding twice to the hydrophobic cavity of EthR from M. tuberculosis. These together fill the entire binding pocket of EthR. We elaborated these fragment hits and developed small molecule inhibitors which have a 100-fold improvement of potency in vitro over the initial fragments. | ||
| - | + | A fragment merging approach towards the development of small molecule inhibitors of Mycobacterium tuberculosis EthR for use as ethionamide boosters.,Nikiforov PO, Surade S, Blaszczyk M, Delorme V, Brodin P, Baulard AR, Blundell TL, Abell C Org Biomol Chem. 2016 Jan 25. PMID:26806381<ref>PMID:26806381</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5f27" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Abell, C]] | [[Category: Abell, C]] | ||
[[Category: Blaszczyk, M]] | [[Category: Blaszczyk, M]] | ||
| - | [[Category: | + | [[Category: Blundell, T L]] |
| - | [[Category: | + | [[Category: Nikiforov, P O]] |
[[Category: Surade, S]] | [[Category: Surade, S]] | ||
| + | [[Category: Ethr]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Repressor]] | ||
| + | [[Category: Transcription]] | ||
Revision as of 15:35, 3 February 2016
Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium Tuberculosis in complex with compound 2 at 1.68A resolution
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