View source for 8otl


==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]] 2.11&Aring;' 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]] 2.108&#8491;</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8otl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Chebaiki M]]
[[Category: Lherbet C]]
[[Category: Maveyraud L]]
[[Category: Mourey L]]
[[Category: Tamhaev R]]