5f08: Difference between revisions
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==Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium tuberculosis in complex with compound 14 at 1.92A resolution== | ==Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium tuberculosis in complex with compound 14 at 1.92A resolution== | ||
<StructureSection load='5f08' size='340' side='right' caption='[[5f08]], [[Resolution|resolution]] 1.92Å' scene=''> | <StructureSection load='5f08' size='340' side='right'caption='[[5f08]], [[Resolution|resolution]] 1.92Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f08]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F08 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5f08]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F08 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5TG:~{TERT}-BUTYL+~{N}-METHYL-~{N}-[[4-[4-(3-OXIDANYLIDENE-3-PYRROLIDIN-1-YL-PROPYL)PIPERIDIN-1-YL]PHENYL]METHYL]CARBAMATE'>5TG</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.92Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5TG:~{TERT}-BUTYL+~{N}-METHYL-~{N}-[[4-[4-(3-OXIDANYLIDENE-3-PYRROLIDIN-1-YL-PROPYL)PIPERIDIN-1-YL]PHENYL]METHYL]CARBAMATE'>5TG</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=5f08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f08 OCA], [https://pdbe.org/5f08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f08 RCSB], [https://www.ebi.ac.uk/pdbsum/5f08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f08 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ETHR_MYCTU ETHR_MYCTU] Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).<ref>PMID:10869356</ref> <ref>PMID:10944230</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 18: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5f08" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5f08" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Complement C3 3D structures|Complement C3 3D structures]] | |||
*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mycobacterium tuberculosis CDC1551]] | ||
[[Category: | [[Category: Abell C]] | ||
[[Category: | [[Category: Blaszczyk M]] | ||
[[Category: | [[Category: Blundell TL]] | ||
[[Category: | [[Category: Nikiforov PO]] | ||
[[Category: | [[Category: Surade S]] | ||
Latest revision as of 11:37, 12 July 2023
Structure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium tuberculosis in complex with compound 14 at 1.92A resolutionStructure of Transcriptional Regulatory Repressor Protein - EthR from Mycobacterium tuberculosis in complex with compound 14 at 1.92A resolution
Structural highlights
FunctionETHR_MYCTU Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).[1] [2] Publication Abstract from PubMedWith 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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