@article{ba7d016e97854521a3ce2dd7cdfc6550,
title = "Structure of the cytochrome aa3-600 heme-copper menaquinol oxidase bound to inhibitor HQNO shows TM0 is part of the quinol binding site",
abstract = "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-{\AA}-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.",
keywords = "Electron transport chain, Heme-copper oxidoreductase, Proton pumping",
author = "Jingjing Xu and Ziqiao Ding and Bing Liu and Yi, {Sophia M.} and Jiao Li and Zhengguang Zhang and Yuchen Liu and Jin Li and Liu Liu and Aiwu Zhou and Gennis, {Robert B.} and Jiapeng Zhu",
note = "Funding Information: We thank Dr. Andrew Leslie for advice on the manuscript and the Shanghai Synchrotron Radiation Facility beamline BL17U1 for access to their synchrotron facilities. This work was supported by National Key R & D Plan for Precision Medicine Research Grant 2016YFC0905900; the Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine); and Jiangsu Specially Appointed Professor Funding. Portions of the research were also supported by Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Sciences, US Department of Energy Grant DEFG02-87ER13716 (to R.B.G.). Funding Information: ACKNOWLEDGMENTS. We thank Dr. Andrew Leslie for advice on the manuscript and the Shanghai Synchrotron Radiation Facility beamline BL17U1 for access to their synchrotron facilities. This work was supported by National Key R & D Plan for Precision Medicine Research Grant 2016YFC0905900; the Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine); and Jiangsu Specially Appointed Professor Funding. Portions of the research were also supported by Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Sciences, US Department of Energy Grant DE-FG02-87ER13716 (to R.B.G.). Publisher Copyright: {\textcopyright} 2020 National Academy of Sciences. All rights reserved.",
year = "2020",
month = jan,
day = "14",
doi = "10.1073/pnas.1915013117",
language = "English (US)",
volume = "117",
pages = "872--876",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "2",
}