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==== | ==Cryo-EM structure of apo hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV== | ||
<StructureSection load='7e1v' size='340' side='right'caption='[[7e1v]]' scene=''> | <StructureSection load='7e1v' size='340' side='right'caption='[[7e1v]], [[Resolution|resolution]] 2.68Å' 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'>[[7e1v]] 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=7E1V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E1V 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=7e1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e1v OCA], [https://pdbe.org/7e1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e1v RCSB], [https://www.ebi.ac.uk/pdbsum/7e1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e1v ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9Y0:(2R)-3-(((2-aminoethoxy)(hydroxy)phosphoryl)oxy)-2-(palmitoyloxy)propyl+(E)-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=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=7e1v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e1v OCA], [https://pdbe.org/7e1v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e1v RCSB], [https://www.ebi.ac.uk/pdbsum/7e1v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e1v ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/A0R057_MYCS2 A0R057_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 QcrBThr(313) and QcrBGlu(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. pii: 69418. 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 7e1v" style="background-color:#fffaf0;"></div> | |||
== 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]] | |||
Revision as of 07:38, 8 September 2022
Cryo-EM structure of apo hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIVCryo-EM structure of apo hybrid respiratory supercomplex consisting of Mycobacterium tuberculosis complexIII and Mycobacterium smegmatis complexIV
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 QcrBThr(313) and QcrBGlu(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. pii: 69418. doi: 10.7554/eLife.69418. PMID:34819223[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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