Characterization of the Pseudomonas aeruginosa NQR complex, a bacterial proton pump with roles in autopoisoning resistance.
J Biol Chem
; 293(40): 15664-15677, 2018 10 05.
Article
en En
| MEDLINE
| ID: mdl-30135204
ABSTRACT
Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a large number of nosocomial infections. The P. aeruginosa respiratory chain contains the ion-pumping NADHubiquinone oxidoreductase (NQR). This enzyme couples the transfer of electrons from NADH to ubiquinone to the pumping of sodium ions across the cell membrane, generating a gradient that drives essential cellular processes in many bacteria. In this study, we characterized P. aeruginosa NQR (Pa-NQR) to elucidate its physiologic function. Our analyses reveal that Pa-NQR, in contrast with NQR homologues from other bacterial species, is not a sodium pump, but rather a completely new form of proton pump. Homology modeling and molecular dynamics simulations suggest that cation selectivity could be determined by the exit ion channels. We also show that Pa-NQR is resistant to the inhibitor 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO). HQNO is a quinolone secreted by P. aeruginosa during infection that acts as a quorum sensing agent and also has bactericidal properties against other bacteria. Using comparative analysis and computational modeling of the ubiquinone-binding site, we identified the specific residues that confer resistance toward this inhibitor. In summary, our findings indicate that Pa-NQR is a proton pump rather than a sodium pump and is highly resistant against the P. aeruginosa-produced compound HQNO, suggesting an important role in the adaptation against autotoxicity. These results provide a deep understanding of the metabolic role of NQR in P. aeruginosa and provide insight into the structural factors that determine the functional specialization in this family of respiratory complexes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Protones
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Pseudomonas aeruginosa
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Proteínas Bacterianas
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Ubiquinona
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Complejo I de Transporte de Electrón
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Electrones
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Biol Chem
Año:
2018
Tipo del documento:
Article