NADH:Quinone Oxidoreductase Mechanisms in Pathogenic Bacteria

NADH:quinone oxidoreductases (NQRs) constitute the primary entry point for electrons into the respiratory chains of many pathogenic bacteria. These multi-subunit membrane complexes catalyse the oxidation of NADH and reduction of quinone to quinol, coupling redox chemistry with active ion translocation to generate electrochemical gradients. The resulting sodium- or proton-motive forces drive ATP synthesis, nutrient uptake, motility and virulence. Structural studies have revealed a cascade of distinct cofactors—FAD, iron-sulphur centres, FMNs and riboflavin—arranged to shuttle electrons across the membrane. Conformational coupling between redox centres and ion-binding sites orchestrates the timing of ion release, while species-specific variations confer selectivity for Na+ or H+ and resistance to endogenous inhibitors. Understanding these mechanisms is critical for the design of novel antimicrobial strategies targeting bacterial bioenergetics.

Research from Nature Portfolio

Recent studies have elucidated the dynamic structural changes underpinning the coupling of electron transfer to Na+ translocation in the Na+-pumping NQR of Vibrio cholerae. A series of cryo-EM and X-ray snapshots captured discrete steps of the catalytic cycle, revealing how the redox state of an intramembranous [2Fe-2S] cluster triggers large movements of a peripheral subunit that acts as an electron-transfer switch. These conformational shifts open and close the sodium-binding chamber, synchronising Na+ release with quinone reduction. The work provides a detailed molecular framework for the design of inhibitors that disrupt energy transduction in pathogenic species.

NADH:Quinone Oxidoreductase Mechanisms in Pathogenic Bacteria publication trend

The graph below shows the total number of articles in nadh:quinone oxidoreductase mechanisms in pathogenic bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

NADH:quinone oxidoreductase (NQR): A membrane-embedded enzyme complex that couples NADH oxidation to quinone reduction with ion pumping.

Conformational coupling: A mechanistic process by which changes in protein shape link redox reactions to ion translocation.

Electrochemical gradient: A transmembrane difference in ion concentration and charge used to power cellular processes.

Flavinylation: The covalent attachment of a flavin cofactor (FMN or FAD) to a protein, essential for redox activity.

Ubiquinone: A lipid-soluble quinone that shuttles electrons within the membrane arm of the respiratory chain.

References

1. Conformational coupling of redox-driven Na+-translocation in Vibrio cholerae NADH:quinone oxidoreductase. Nature Structural & Molecular Biology (2023).
2. Identification of complex III, NQR, and SDH as primary bioenergetic enzymes during the stationary phase of Pseudomonas aeruginosa cultured in urine-like conditions. Frontiers in Microbiology (2024).
3. Characterization of the Pseudomonas aeruginosa NQR complex, a bacterial proton pump with roles in autopoisoning resistance. Journal of Biological Chemistry (2018).
4. The Electron Transfer Pathway of the Na+-pumping NADH:Quinone Oxidoreductase from Vibrio cholerae *. Journal of Biological Chemistry (2009).