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8otl
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==structure of InhA from Mycobacterium tuberculosis in complex with 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol== | |
| + | <StructureSection load='8otl' size='340' side='right'caption='[[8otl]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8otl]] is a 6 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=8OTL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OTL 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]] 2.108Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=VZE:5-[[octyl-[[4-(2-oxidanylphenoxy)phenyl]methyl]amino]methyl]-2-phenoxy-phenol'>VZE</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=8otl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8otl OCA], [https://pdbe.org/8otl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8otl RCSB], [https://www.ebi.ac.uk/pdbsum/8otl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8otl ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a worldwide scourge with more than 10 million people affected yearly. Among the proteins essential for the survival of Mtb, InhA has been and is still clinically validated as a therapeutic target. A new family of direct diaryl ether inhibitors, not requiring prior activation by the catalase peroxidase enzyme KatG, has been designed with the ambition of fully occupying the InhA substrate-binding site. Thus, eleven compounds, featuring three pharmacophores within the same molecule, were synthesized. One of them, 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol (compound 21), showed good inhibitory activity against InhA with IC(50) of 0.70 microM. The crystal structure of compound 21 in complex with InhA/NAD(+) showed how the molecule fills the substrate-binding site as well as the minor portal of InhA. This study represents a further step towards the design of new inhibitors of InhA. | ||
| - | + | Exploring the plasticity of the InhA substrate-binding site using new diaryl ether inhibitors.,Tamhaev R, Grosjean E, Ahamed H, Chebaiki M, Rodriguez F, Recchia D, Degiacomi G, Pasca MR, Maveyraud L, Mourey L, Lherbet C Bioorg Chem. 2024 Feb;143:107032. doi: 10.1016/j.bioorg.2023.107032. Epub 2023 , Dec 12. PMID:38128204<ref>PMID:38128204</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8otl" style="background-color:#fffaf0;"></div> |
| - | [[Category: Lherbet | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Chebaiki M]] | ||
| + | [[Category: Lherbet C]] | ||
| + | [[Category: Maveyraud L]] | ||
| + | [[Category: Mourey L]] | ||
| + | [[Category: Tamhaev R]] | ||
Current revision
structure of InhA from Mycobacterium tuberculosis in complex with 5-(((4-(2-hydroxyphenoxy)benzyl)(octyl)amino)methyl)-2-phenoxyphenol
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