Structure of the cytochrome aa3-600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site

Jingjing Xu, Ziqiao Ding, Bing Liu, Sophia M. Yi, Jiao Li, Zhengguang Zhang, Yuchen Liu, Jin Li, Liu Liu, Aiwu Zhou, Robert B. Gennis, Jiapeng Zhu

Research output: Contribution to journalArticlepeer-review


Virtually all proton-pumping terminal respiratory oxygen reductases are members of the heme-copper oxidoreductase superfamily. Most of these enzymes use reduced cytochrome c as a source of electrons, but a group of enzymes have evolved to directly oxidize membrane-bound quinols, usually menaquinol or ubiquinol. All of the quinol oxidases have an additional transmembrane helix (TM0) in subunit I that is not present in the related cytochrome c oxidases. The current work reports the 3.6-Å-resolution X-ray structure of the cytochrome aa3-600 menaquinol oxidase from Bacillus subtilis containing 1 equivalent of menaquinone. The structure shows that TM0 forms part of a cleft to accommodate the menaquinol-7 substrate. Crystals which have been soaked with the quinol-analog inhibitor HQNO (N-oxo-2-heptyl-4-hydroxyquinoline) or 3-iodo-HQNO reveal a single binding site where the inhibitor forms hydrogen bonds to amino acid residues shown previously by spectroscopic methods to interact with the semiquinone state of menaquinone, a catalytic intermediate.

Original languageEnglish (US)
Pages (from-to)872-876
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - Jan 14 2020


  • Electron transport chain
  • Heme-copper oxidoreductase
  • Proton pumping

ASJC Scopus subject areas

  • General

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