9wcx: Difference between revisions

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'''Unreleased structure'''


The entry 9wcx is ON HOLD  until Paper Publication
==Cryo-EM structure of the Mycobacterium abscessus cytochrome bcc:aa3 supercomplex==
<StructureSection load='9wcx' size='340' side='right'caption='[[9wcx]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wcx]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacteroides_abscessus Mycobacteroides abscessus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9WCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WCX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.66&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9XX:[(2~{S})-1-hexadecanoyloxypropan-2-yl]+(10~{S})-10-methyloctadecanoate'>9XX</scene>, <scene name='pdbligand=9Y0:(2R)-3-{[(R)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(hexadecanoyloxy)propyl+(9Z)-octadec-9-enoate'>9Y0</scene>, <scene name='pdbligand=9YF:[(2~{R})-2-hexadecanoyloxy-3-[oxidanyl-[(2~{S},3~{R},5~{R},6~{R})-2,3,4,5,6-pentakis(oxidanyl)cyclohexyl]oxy-phosphoryl]oxy-propyl]+(9~{S})-9-methyloctadecanoate'>9YF</scene>, <scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEA:HEME-A'>HEA</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MQ9:MENAQUINONE-9'>MQ9</scene>, <scene name='pdbligand=OXY:OXYGEN+MOLECULE'>OXY</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=9wcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wcx OCA], [https://pdbe.org/9wcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wcx RCSB], [https://www.ebi.ac.uk/pdbsum/9wcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wcx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/B1MDZ6_MYCA9 B1MDZ6_MYCA9] Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B.[ARBA:ARBA00025218][RuleBase:RU363061]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cytochrome bcc:aa(3) oxidase is the target of telacebec, a clinically advanced drug developed for Mycobacterium tuberculosis. However, telacebec is inactive against Mycobacterium abscessus, an opportunistic pathogen increasingly linked to chronic pulmonary infections and notoriously known for intrinsic resistance to numerous antibiotics. Here, we report the 2.6 A cryo-electron microscopy structure of the M. abscessus bcc:aa(3) cytochrome oxidase supercomplex, revealing key pathways and the evolution of the mycobacterial QcrB menaquinol-binding cavity. Structure-guided mutagenesis identified polymorphisms that modulate telacebec binding and potency in both M. abscessus and Mycobacterium smegmatis. Leveraging these insights, we designed ND-011458, a QcrB inhibitor with potent activity against M. abscessus and being bactericidal in combination with Clofazimine. The 2.26 A inhibitor-bound structure elucidates its binding mode and provides a framework for the design of next-generation inhibitors for M. abscessus pulmonary diseases.


Authors:  
The Mycobacterium abscessus cytochrome bcc:aa(3) oxidase structure paves the way for an agent targeting subunit QcrB.,Mathiyazakan V, Tan EXY, Moraski G, Basak S, Saw WG, Pethe K, Gruber G Nat Commun. 2026 Apr 3;17(1):4821. doi: 10.1038/s41467-026-70805-5. PMID:41932870<ref>PMID:41932870</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9wcx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacteroides abscessus]]
[[Category: Gruber G]]
[[Category: Mathiyazakan V]]
Retrieved from "https://proteopedia.org/9wcx"