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==Structure of bacterial type II NADH dehydrogenase from Caldalkalibacillus thermarum complexed with a quinone inhibitor HQNO at 2.8A resolution==
<StructureSection load='6bdo' size='340' side='right'caption='[[6bdo]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bdo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Caldalkalibacillus_thermarum_TA2.A1 Caldalkalibacillus thermarum TA2.A1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BDO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BDO 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=HQO:2-HEPTYL-4-HYDROXY+QUINOLINE+N-OXIDE'>HQO</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=6bdo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bdo OCA], [https://pdbe.org/6bdo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bdo RCSB], [https://www.ebi.ac.uk/pdbsum/6bdo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bdo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F5L3B8_CALTT F5L3B8_CALTT] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Type II NADH:quinone oxidoreductase (NDH-2) is a proposed drug-target of major pathogenic microorganisms such as Mycobacterium tuberculosis and Plasmodium falciparum. Many NDH-2 inhibitors have been identified, but rational drug development is impeded by the lack of information regarding their mode of action and associated inhibitor-bound NDH-2 structure. We have determined the crystal structure of NDH-2 complexed with a quinolone inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). HQNO is nested into the slot-shaped tunnel of the Q-site, in which the quinone-head group is clamped by Q317 and I379 residues, and hydrogen-bonds to FAD. The interaction of HQNO with bacterial NDH-2 is very similar to the native substrate ubiquinone (UQ1) interactions in the yeast Ndi1-UQ1 complex structure, suggesting a conserved mechanism for quinone binding. Further, the structural analysis provided insight how modifications of quinolone scaffolds improve potency (e.g. quinolinyl pyrimidine derivatives) and suggests unexplored target space for the rational design of new NDH-2 inhibitors.

Structure of the NDH-2 - HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors.,Petri J, Shimaki Y, Jiao W, Bridges HR, Russell ER, Parker EJ, Aragao D, Cook GM, Nakatani Y Biochim Biophys Acta. 2018 Jul;1859(7):482-490. doi:, 10.1016/j.bbabio.2018.03.014. Epub 2018 Apr 3. PMID:29621505<ref>PMID:29621505</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6bdo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caldalkalibacillus thermarum TA2 A1]]
[[Category: Large Structures]]
[[Category: Aragao D]]
[[Category: Cook GM]]
[[Category: Nakatani Y]]