4A5M

Redox regulator HypR in its oxidized form

4A5M の概要

• エントリーDOI: 10.2210/pdb4a5m/pdb
• 関連するPDBエントリー: 4A5N
• 分子名称: UNCHARACTERIZED HTH-TYPE TRANSCRIPTIONAL REGULATOR YYBR, 1,2-ETHANEDIOL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: transcription, activator, dna-binding
• 由来する生物種: BACILLUS SUBTILIS
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 125257.17

構造登録者

Palm, G.J.,Waack, P.,Read, R.J.,Hinrichs, W. (登録日: 2011-10-26, 公開日: 2012-01-11, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3 Å)