4A5M

Redox regulator HypR in its oxidized form

Summary for 4A5M

• Entry DOI: 10.2210/pdb4a5m/pdb
• Related: 4A5N
• Descriptor: UNCHARACTERIZED HTH-TYPE TRANSCRIPTIONAL REGULATOR YYBR, 1,2-ETHANEDIOL, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: transcription, activator, dna-binding
• Biological source: BACILLUS SUBTILIS
• Total number of polymer chains: 8
• Total formula weight: 125257.17

Authors

Palm, G.J.,Waack, P.,Read, R.J.,Hinrichs, W. (deposition date: 2011-10-26, release date: 2012-01-11, Last modification date: 2024-10-23)

Primary citation

Palm, G.J.,Chi, B.K.,Waack, P.,Gronau, K.,Becher, D.,Albrecht, D.,Hinrichs, W.,Read, R.J.,Antelmann, H.
Structural Insights Into the Redox-Switch Mechanism of the Marr/Duf24-Type Regulator Hypr
Nucleic Acids Res., 40:4178-, 2012

PubMed Abstract: Bacillus subtilis encodes redox-sensing MarR-type regulators of the OhrR and DUF24-families that sense organic hydroperoxides, diamide, quinones or aldehydes via thiol-based redox-switches. In this article, we characterize the novel redox-sensing MarR/DUF24-family regulator HypR (YybR) that is activated by disulphide stress caused by diamide and NaOCl in B. subtilis. HypR controls positively a flavin oxidoreductase HypO that confers protection against NaOCl stress. The conserved N-terminal Cys14 residue of HypR has a lower pK(a) of 6.36 and is essential for activation of hypO transcription by disulphide stress. HypR resembles a 2-Cys-type regulator that is activated by Cys14-Cys49' intersubunit disulphide formation. The crystal structures of reduced and oxidized HypR proteins were resolved revealing structural changes of HypR upon oxidation. In reduced HypR a hydrogen-bonding network stabilizes the reactive Cys14 thiolate that is 8-9 Å apart from Cys49'. HypR oxidation breaks these H-bonds, reorients the monomers and moves the major groove recognition α4 and α4' helices ∼4 Å towards each other. This is the first crystal structure of a redox-sensing MarR/DUF24 family protein in bacteria that is activated by NaOCl stress. Since hypochloric acid is released by activated macrophages, related HypR-like regulators could function to protect pathogens against the host immune defense.

PubMed: 22238377
DOI: 10.1093/NAR/GKR1316

Experimental method

X-RAY DIFFRACTION (3 Å)