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==== | ==Cryo-EM structure of hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV in presence of TB47== | ||
<StructureSection load='7e1x' size='340' side='right'caption='[[7e1x]]' scene=''> | <StructureSection load='7e1x' size='340' side='right'caption='[[7e1x]], [[Resolution|resolution]] 2.93Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7e1x]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] and [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_51 Mycolicibacterium smegmatis MC2 51]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E1X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E1X FirstGlance]. <br> | ||
</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=7e1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e1x OCA], [https://pdbe.org/7e1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e1x RCSB], [https://www.ebi.ac.uk/pdbsum/7e1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e1x ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.93Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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:(2R)-2-(hexadecanoyloxy)-3-{[(S)-hydroxy{[(1R,2R,3R,4R,5R,6S)-2,3,4,5,6-pentahydroxycyclohexyl]oxy}phosphoryl]oxy}propyl+(9S)-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=HV0:5-methoxy-2-methyl-~{N}-[[4-[4-[4-(trifluoromethyloxy)phenyl]piperidin-1-yl]phenyl]methyl]pyrazolo[1,5-a]pyridine-3-carboxamide'>HV0</scene>, <scene name='pdbligand=MQ9:MENAQUINONE-9'>MQ9</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=7e1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e1x OCA], [https://pdbe.org/7e1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e1x RCSB], [https://www.ebi.ac.uk/pdbsum/7e1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e1x ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0R1B6_MYCS2 A0R1B6_MYCS2] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome bcc complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome bcc complex from these pathogenic mycobacteria. Here, we report the structures of Mycobacterium tuberculosis cytochrome bcc alone (2.68 A resolution) and in complex with clinical drug candidates Q203 (2.67 A resolution) and TB47 (2.93 A resolution) determined by single-particle cryo-electron microscopy. M. tuberculosis cytochrome bcc forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of (QcrB)Thr(313) and (QcrB)Glu(314), residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome bcc inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections. | |||
Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates.,Zhou S, Wang W, Zhou X, Zhang Y, Lai Y, Tang Y, Xu J, Li D, Lin J, Yang X, Ran T, Chen H, Guddat LW, Wang Q, Gao Y, Rao Z, Gong H Elife. 2021 Nov 25;10:e69418. doi: 10.7554/eLife.69418. PMID:34819223<ref>PMID:34819223</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7e1x" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cytochrome bc1 3D structures|Cytochrome bc1 3D structures]] | |||
*[[Cytochrome c oxidase 3D structures|Cytochrome c oxidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Z | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Mycolicibacterium smegmatis MC2 51]] | |||
[[Category: Gao Y]] | |||
[[Category: Gong H]] | |||
[[Category: Rao Z]] | |||
[[Category: Wang W]] | |||
[[Category: Zhou S]] | |||
Latest revision as of 09:13, 21 November 2024
Cryo-EM structure of hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV in presence of TB47Cryo-EM structure of hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV in presence of TB47
Structural highlights
FunctionPublication Abstract from PubMedPathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome bcc complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome bcc complex from these pathogenic mycobacteria. Here, we report the structures of Mycobacterium tuberculosis cytochrome bcc alone (2.68 A resolution) and in complex with clinical drug candidates Q203 (2.67 A resolution) and TB47 (2.93 A resolution) determined by single-particle cryo-electron microscopy. M. tuberculosis cytochrome bcc forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of (QcrB)Thr(313) and (QcrB)Glu(314), residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome bcc inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections. Structure of Mycobacterium tuberculosis cytochrome bcc in complex with Q203 and TB47, two anti-TB drug candidates.,Zhou S, Wang W, Zhou X, Zhang Y, Lai Y, Tang Y, Xu J, Li D, Lin J, Yang X, Ran T, Chen H, Guddat LW, Wang Q, Gao Y, Rao Z, Gong H Elife. 2021 Nov 25;10:e69418. doi: 10.7554/eLife.69418. PMID:34819223[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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