8AJJ

Crystal structure of the disulfide reductase MerA from Staphylococcus aureus

8AJJ の概要

• エントリーDOI: 10.2210/pdb8ajj/pdb
• 分子名称: Dihydrolipoamide dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, HISTIDINE, ... (4 entities in total)
• 機能のキーワード: mera, disulfide reductase, oxidoreductase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 200590.92

構造登録者

Weiland, P.,Altegoer, F.,Bange, G. (登録日: 2022-07-28, 公開日: 2023-03-01, 最終更新日: 2024-10-23)

主引用文献

Shearer, H.L.,Loi, V.V.,Weiland, P.,Bange, G.,Altegoer, F.,Hampton, M.B.,Antelmann, H.,Dickerhof, N.
MerA functions as a hypothiocyanous acid reductase and defense mechanism in Staphylococcus aureus.
Mol.Microbiol., 119:456-470, 2023

PubMed Abstract: The major pathogen Staphylococcus aureus has to cope with host-derived oxidative stress to cause infections in humans. Here, we report that S. aureus tolerates high concentrations of hypothiocyanous acid (HOSCN), a key antimicrobial oxidant produced in the respiratory tract. We discovered that the flavoprotein disulfide reductase (FDR) MerA protects S. aureus from this oxidant by functioning as a HOSCN reductase, with its deletion sensitizing bacteria to HOSCN. Crystal structures of homodimeric MerA (2.4 Å) with a Cys -Cys intramolecular disulfide, and reduced MerACys S (1.6 Å) showed the FAD cofactor close to the active site, supporting that MerA functions as a group I FDR. MerA is controlled by the redox-sensitive repressor HypR, which we show to be oxidized to intermolecular disulfides under HOSCN stress, resulting in its inactivation and derepression of merA transcription to promote HOSCN tolerance. Our study highlights the HOSCN tolerance of S. aureus and characterizes the structure and function of MerA as a major HOSCN defense mechanism. Crippling the capacity to respond to HOSCN may be a novel strategy for treating S. aureus infections.

PubMed: 36779383
DOI: 10.1111/mmi.15035

実験手法

X-RAY DIFFRACTION (2.4 Å)