4XWS

OxyR regulatory domain C199D mutant from pseudomonas aeruginosa

4XWS の概要

• エントリーDOI: 10.2210/pdb4xws/pdb
• 関連するPDBエントリー: 4X6G 4Y0M
• 分子名称: OxyR (1 entity in total)
• 機能のキーワード: oxyr, peroxide, transcription regulator, lysr, dna binding protein
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100571.70

構造登録者

Jo, I.,Kim, J.S.,Ha, N.C. (登録日: 2015-01-29, 公開日: 2015-04-29, 最終更新日: 2024-03-20)

主引用文献

Jo, I.,Chung, I.Y.,Bae, H.W.,Kim, J.S.,Song, S.,Cho, Y.H.,Ha, N.C.
Structural details of the OxyR peroxide-sensing mechanism
Proc.Natl.Acad.Sci.USA, 112:6443-6448, 2015

PubMed Abstract: OxyR, a bacterial peroxide sensor, is a LysR-type transcriptional regulator (LTTR) that regulates the transcription of defense genes in response to a low level of cellular H2O2. Consisting of an N-terminal DNA-binding domain (DBD) and a C-terminal regulatory domain (RD), OxyR senses H2O2 with conserved cysteine residues in the RD. However, the precise mechanism of OxyR is not yet known due to the absence of the full-length (FL) protein structure. Here we determined the crystal structures of the FL protein and RD of Pseudomonas aeruginosa OxyR and its C199D mutant proteins. The FL crystal structures revealed that OxyR has a tetrameric arrangement assembled via two distinct dimerization interfaces. The C199D mutant structures suggested that new interactions that are mediated by cysteine hydroxylation induce a large conformational change, facilitating intramolecular disulfide-bond formation. More importantly, a bound H2O2 molecule was found near the Cys199 site, suggesting the H2O2-driven oxidation mechanism of OxyR. Combined with the crystal structures, a modeling study suggested that a large movement of the DBD is triggered by structural changes in the regulatory domains upon oxidation. Taken together, these findings provide novel concepts for answering key questions regarding OxyR in the H2O2-sensing and oxidation-dependent regulation of antioxidant genes.

PubMed: 25931525
DOI: 10.1073/pnas.1424495112

実験手法

X-RAY DIFFRACTION (3.006 Å)