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TitleMycobacterial respiratory chain enzymes and growth are inhibited by decylubiquinone.
Journal, issue, pagesCommun Biol, Vol. 9, Issue 1, Page 43, Year 2025
Publish dateDec 10, 2025
AuthorsSylwia Król / Terezia Kovalova / Mateusz Janczak / Sadaf Kalsum / Mira Akber / Martin Högbom / Susanna Brighenti / Pia Ädelroth / Peter Brzezinski /
PubMed AbstractAerobic organisms obtain energy by linking electron transfer from NADH to O, through the respiratory chain, to transmembrane proton translocation. In mycobacteria the respiratory chain is branched; ...Aerobic organisms obtain energy by linking electron transfer from NADH to O, through the respiratory chain, to transmembrane proton translocation. In mycobacteria the respiratory chain is branched; the membrane-bound electron carrier menaquinol (MQH) donates electrons either to the O-reducing cytochrome bd or a supercomplex that is composed of a complex (C) III dimer flanked by two CIVs. Here, we measured the dimethyl-naphthoquinone (DMNQH a menaquinol analogue) oxidation:O reduction activities of the CIIICIV supercomplex and cytochrome bd in the presence of an analogue (decylubiquinone, DCQ) of the mammalian electron carrier, ubiquinol. The data show that DCQH inhibits both the CIIICIV and cytochrome bd activities, suggesting that DCQ/DCQH interferes with both branches of the respiratory chain. Cryo-EM data of the M. smegmatis supercomplex shows that oxidized DCQ binds in the electron donor site (Q) of CIII. Accordingly, growth of M. smegmatis cells was impaired in the presence of DCQ. Remarkably, DCQ also impairs intracellular growth of virulent M. tuberculosis cells in human primary macrophages suggesting that the compound could potentially be used as an adjuvant during tuberculosis disease treatment.
External linksCommun Biol / PubMed:41372535 / PubMed Central
MethodsEM (single particle)
Resolution2.5 Å
Structure data

EMDB-53065, PDB-9qef:
Respiratory supercomplex from Mycobacterium smegmatis with decylubiquinone
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-HEC:
HEME C

ChemComp-MQ9:
MENAQUINONE-9


ChemComp, No image

ChemComp-WUO:
Unknown entry

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-IZL:
[(2~{R})-3-[[(1~{S},2~{R},3~{S},4~{S},5~{R},6~{R})-2-[(2~{R},3~{S},4~{S},5~{S},6~{R})-6-[[(2~{S},3~{S},4~{S},5~{S},6~{R})-6-[[(2~{S},3~{S},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3-[(2~{R},3~{S},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-4,5-bis(oxidanyl)oxan-2-yl]oxymethyl]-3,4,5-tris(oxidanyl)oxan-2-yl]oxymethyl]-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-3,4,5-tris(oxidanyl)-6-[(2~{R},3~{S},4~{S},5~{S},6~{R})-3,4,5-tris(oxidanyl)-6-(undecanoyloxymethyl)oxan-2-yl]oxy-cyclohexyl]oxy-oxidanyl-phosphoryl]oxy-2-undecanoyloxy-propyl] (10~{R})-10-methyldodecanoate

ChemComp-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

ChemComp-7PH:
(1R)-2-(dodecanoyloxy)-1-[(phosphonooxy)methyl]ethyl tetradecanoate

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-PLM:
PALMITIC ACID

ChemComp-9XX:
(2S)-1-(hexadecanoyloxy)propan-2-yl (10S)-10-methyloctadecanoate

ChemComp-TRD:
TRIDECANE

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM

ChemComp-HEA:
HEME-A

ChemComp-CU:
COPPER (II) ION

ChemComp-MG:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-DCQ:
2-decyl-5,6-dimethoxy-3-methylcyclohexa-2,5-diene-1,4-dione

ChemComp-HOH:
WATER

Source
  • mycolicibacterium smegmatis (bacteria)
KeywordsELECTRON TRANSPORT / RESPIRATORY SUPERCOMPLEX / MEMBRANE PROTEIN / ACTINOBACTERIA

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