8AJK

Crystal structure of a C43S variant from the disulfide reductase MerA from Staphylococcus aureus

Summary for 8AJK

• Entry DOI: 10.2210/pdb8ajk/pdb
• Descriptor: FAD-containing oxidoreductase, GLYCEROL, FLAVIN-ADENINE DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: mera, disulfide reductase, oxidoreductase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 101113.67

Authors

Weiland, P.,Altegoer, F.,Bange, G. (deposition date: 2022-07-28, release date: 2023-03-01, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)