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Structural snapshots of OxyR reveal the peroxidatic mechanism of H2O2 sensing.


ABSTRACT: Hydrogen peroxide (H2O2) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward H2O2 One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces H2O2 In this study, we present crystallographic evidence for the H2O2-sensing mechanism and H2O2-dependent structural transition of Corynebacterium glutamicum OxyR by capturing the reduced and H2O2-bound structures of a serine mutant of the peroxidatic cysteine, and the full-length crystal structure of disulfide-bonded oxidized OxyR. In the H2O2-bound structure, we pinpoint the key residues for the peroxidatic reduction of H2O2, and relate this to mutational assays showing that the conserved active-site residues T107 and R278 are critical for effective H2O2 reduction. Furthermore, we propose an allosteric mode of structural change, whereby a localized conformational change arising from H2O2-induced intramolecular disulfide formation drives a structural shift at the dimerization interface of OxyR, leading to overall changes in quaternary structure and an altered DNA-binding topology and affinity at the catalase promoter region. This study provides molecular insights into the overall OxyR transcription mechanism regulated by H2O2.

SUBMITTER: Pedre B 

PROVIDER: S-EPMC6294878 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Structural snapshots of OxyR reveal the peroxidatic mechanism of H<sub>2</sub>O<sub>2</sub> sensing.

Pedre Brandán B   Young David D   Charlier Daniel D   Mourenza Álvaro Á   Rosado Leonardo Astolfi LA   Marcos-Pascual Laura L   Wahni Khadija K   Martens Edo E   G de la Rubia Alfonso A   Belousov Vsevolod V VV   Mateos Luis M LM   Messens Joris J  

Proceedings of the National Academy of Sciences of the United States of America 20181121 50


Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward H<sub>2</sub>O<sub>2</sub> One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces H<sub>2</sub>O<sub>2</sub> In this study, we present crystallographic evidence for the H<sub>2</sub>O<sub>2</sub>-sensing mech  ...[more]

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