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

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Hydrogen peroxide (H 2O 2) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward H 2O 2. One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces H 2O 2. In this study, we present crystallographic evidence for the H 2O 2-sensing mechanism and H 2O 2-dependent structural transition of Corynebacterium glutamicum OxyR by capturing the reduced and H 2O 2-bound structures of a serine mutant of the peroxidatic cysteine, and the full-length crystal structure of disulfide-bonded oxidized OxyR. In the H 2O 2-bound structure, we pinpoint the key residues for the peroxidatic reduction of H 2O 2, and relate this to mutational assays showing that the conserved active-site residues T107 and R278 are critical for effective H 2O 2 reduction. Furthermore, we propose an allosteric mode of structural change, whereby a localized conformational change arising from H 2O 2induced 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 H 2O 2.

Tijdschrift: Proc Natl Acad Sci USA
ISSN: 0027-8424
Issue: 50
Volume: 115
Pagina's: E11623-E11632
Jaar van publicatie:2018
Trefwoorden:Amino Acid Substitution, Bacterial Proteins/chemistry, Binding Sites/genetics, Catalase/chemistry, Corynebacterium glutamicum/genetics, Crystallography, X-Ray, Genes, Bacterial, Hydrogen Peroxide/metabolism, Kinetics, Mutagenesis, Site-Directed, Oxidation-Reduction, Protein Structure, Quaternary, Transcription Factors/chemistry, Transcription, Genetic
BOF-keylabel:ja
BOF-publication weight:6
CSS-citation score:1
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open