Insights into the ubiquinol/dioxygen binding and proton relay pathways of the alternative oxidase

The alternative oxidase (AOX) is a monotopic diiron carboxylate protein which catalyzes the four-electron reduction of dioxygen to water by ubiquinol. Although we have recently determined the crystal structure of Trypanosoma brucei AOX (TAO) in the presence and absence of ascofuranone (AF) derivativ...

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Veröffentlicht in:Biochimica et biophysica acta. Bioenergetics 2019-05, Vol.1860 (5), p.375-382
Hauptverfasser: Shiba, Tomoo, Inaoka, Daniel Ken, Takahashi, Gen, Tsuge, Chiaki, Kido, Yasutoshi, Young, Luke, Ueda, Satoshi, Balogun, Emmanuel Oluwadare, Nara, Takeshi, Honma, Teruki, Tanaka, Akiko, Inoue, Masayuki, Saimoto, Hiroyuki, Harada, Shigeharu, Moore, Anthony L., Kita, Kiyoshi
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container_end_page 382
container_issue 5
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container_title Biochimica et biophysica acta. Bioenergetics
container_volume 1860
creator Shiba, Tomoo
Inaoka, Daniel Ken
Takahashi, Gen
Tsuge, Chiaki
Kido, Yasutoshi
Young, Luke
Ueda, Satoshi
Balogun, Emmanuel Oluwadare
Nara, Takeshi
Honma, Teruki
Tanaka, Akiko
Inoue, Masayuki
Saimoto, Hiroyuki
Harada, Shigeharu
Moore, Anthony L.
Kita, Kiyoshi
description The alternative oxidase (AOX) is a monotopic diiron carboxylate protein which catalyzes the four-electron reduction of dioxygen to water by ubiquinol. Although we have recently determined the crystal structure of Trypanosoma brucei AOX (TAO) in the presence and absence of ascofuranone (AF) derivatives (which are potent mixed type inhibitors) the mechanism by which ubiquinol and dioxygen binds to TAO remain inconclusive. In this article, ferulenol was identified as the first competitive inhibitor of AOX which has been used to probe the binding of ubiquinol. Surface plasmon resonance reveals that AF is a quasi-irreversible inhibitor of TAO whilst ferulenol binding is completely reversible. The structure of the TAO-ferulenol complex, determined at 2.7 Å, provided insights into ubiquinol binding and has also identified a potential dioxygen molecule bound in a side-on conformation to the diiron center for the first time.
doi_str_mv 10.1016/j.bbabio.2019.03.008
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source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present)
subjects Alternative oxidase
Competitive inhibitor
Ferulenol
Proton relay pathway
Trypanosoma brucei
Ubiquinol/dioxygen binding
title Insights into the ubiquinol/dioxygen binding and proton relay pathways of the alternative oxidase
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