28ir: Difference between revisions

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'''Unreleased structure'''


The entry 28ir is ON HOLD  until Paper Publication
==structure of InhA from Mycobacterium tuberculosis in complex with 4-(4-((4-cyclopropyl-1H-1,2,3-triazol-1-yl)methyl)-2-hydroxyphenoxy)-3-fluorobenzaldehyde (compound 5c)==
<StructureSection load='28ir' size='340' side='right'caption='[[28ir]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[28ir]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=28IR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=28IR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1JZB:4-[4-[(4-cyclopropyl-1,2,3-triazol-1-yl)methyl]-2-oxidanyl-phenoxy]-3-fluoranyl-benzaldehyde'>A1JZB</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=28ir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=28ir OCA], [https://pdbe.org/28ir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=28ir RCSB], [https://www.ebi.ac.uk/pdbsum/28ir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=28ir ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The emergence of drug-resistant Mycobacterium tuberculosis underscores the need for innovative therapeutic strategies targeting essential metabolic pathways. We designed, synthesized, and evaluated a series of dual inhibitors targeting two key enzymes of the mycobacterial FAS-II system, HadAB and InhA. Using a diaryl ether scaffold, six thiosemicarbazone derivatives and their aldehyde intermediates were prepared and tested for enzymatic and antimycobacterial activity. Thiosemicarbazone derivatives and aldehyde intermediates both strongly inhibited InhA, and the thiosemicarbazones additionally potentially inhibited HadAB through covalent interaction with the HadA subunit, supporting the dual-target approach. Several compounds showed low micromolar to submicromolar activity against drug-susceptible and clinical M. tuberculosis strains, including an ethA-deficient mutant. Crystallographic structures of InhA-ligand complexes revealed key binding interactions and clarified inhibition mechanisms. Despite some cytotoxicity concerns, these findings provide a promising basis for developing optimized dual-target inhibitors of the M. tuberculosis FAS-II pathway.


Authors: Tamhaev, R., Lherbet, C., Azema-Despeyroux, J., Mourey, L., Maveyraud, L.
Rational Design of Diaryl Ether-Based Dual Inhibitors Targeting Successive Essential Enzymes HadAB and InhA in Mycobacterium tuberculosis.,Tamhaev R, Recchia D, Zahorszka M, Stelitano G, Chiarelli LR, Rizet J, Rima J, Chebaiki M, Valentin L, Azema-Despeyroux J, Hoffmann P, Preuilh N, Dumais B, Britton S, Degiacomi G, Maveyraud L, Kordulakova J, Pasca MR, Mourey L, Lherbet C J Med Chem. 2026 Jul 7. doi: 10.1021/acs.jmedchem.6c01302. PMID:42415474<ref>PMID:42415474</ref>


Description: structure of InhA from Mycobacterium tuberculosis in complex with 4-(4-((4-cyclopropyl-1H-1,2,3-triazol-1-yl)methyl)-2-hydroxyphenoxy)-3-fluorobenzaldehyde (compound 5c)
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Lherbet, C]]
<div class="pdbe-citations 28ir" style="background-color:#fffaf0;"></div>
[[Category: Tamhaev, R]]
== References ==
[[Category: Azema-Despeyroux, J]]
<references/>
[[Category: Mourey, L]]
__TOC__
[[Category: Maveyraud, L]]
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Azema-Despeyroux J]]
[[Category: Lherbet C]]
[[Category: Maveyraud L]]
[[Category: Mourey L]]
[[Category: Tamhaev R]]
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