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==Mycobacterium tuberculosis InhA in complex with NADH==
==Mycobacterium tuberculosis InhA in complex with NADH==
<StructureSection load='4dre' size='340' side='right' caption='[[4dre]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='4dre' size='340' side='right'caption='[[4dre]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dre]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DRE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DRE FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dre]] is a 1 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=4DRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DRE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</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]] 2.4&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dqu|4dqu]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </span></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=4dre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dre OCA], [https://pdbe.org/4dre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dre RCSB], [https://www.ebi.ac.uk/pdbsum/4dre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dre ProSAT]</span></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=4dre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dre OCA], [http://pdbe.org/4dre PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dre RCSB], [http://www.ebi.ac.uk/pdbsum/4dre PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dre ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU]
Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an important source of antibiotics including potent anti-tuberculosis agents. Here, we describe pyridomycin, a compound produced by Dactylosporangium fulvum with specific cidal activity against mycobacteria. By selecting pyridomycin-resistant mutants of Mycobacterium tuberculosis, whole-genome sequencing and genetic validation, we identified the NADH-dependent enoyl- (Acyl-Carrier-Protein) reductase InhA as the principal target and demonstrate that pyridomycin inhibits mycolic acid synthesis in M. tuberculosis. Furthermore, biochemical and structural studies show that pyridomycin inhibits InhA directly as a competitive inhibitor of the NADH-binding site, thereby identifying a new, druggable pocket in InhA. Importantly, the most frequently encountered isoniazid-resistant clinical isolates remain fully susceptible to pyridomycin, thus opening new avenues for drug development. --&gt;See accompanying article http://dx.doi.org/10.1002/emmm.201201811.
 
Towards a new tuberculosis drug: pyridomycin - nature's isoniazid.,Hartkoorn RC, Sala C, Neres J, Pojer F, Magnet S, Mukherjee R, Uplekar S, Boy-Rottger S, Altmann KH, Cole ST EMBO Mol Med. 2012 Sep 17. doi: 10.1002/emmm.201201689. PMID:22987724<ref>PMID:22987724</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dre" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]]
*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Boy, S]]
[[Category: Large Structures]]
[[Category: Cole, S T]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Hartkoorn, R C]]
[[Category: Boy S]]
[[Category: Pojer, F]]
[[Category: Cole ST]]
[[Category: Enoyl-acp reductase]]
[[Category: Hartkoorn RC]]
[[Category: Oxidoreductase]]
[[Category: Pojer F]]

Latest revision as of 10:54, 1 March 2024

Mycobacterium tuberculosis InhA in complex with NADH

4dre, resolution 2.40Å

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