Characterization of the Pseudomonas aeruginosa NQR complex, a bacterial proton pump with roles in autopoisoning resistance.
In: Journal of Biological Chemistry, Jg. 293 (2018-10-05), Heft 40, S. 15664-15677
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Zugriff:
Pseudomonas aeruginosa is a Gram-negative bacterium responsible for a large number of nosocomial infections. The P. aeruginosa respiratory chain contains the ion-pumping NADH:ubiquinone 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. [ABSTRACT FROM AUTHOR]
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Characterization of the Pseudomonas aeruginosa NQR complex, a bacterial proton pump with roles in autopoisoning resistance.
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Autor/in / Beteiligte Person: | Raba, Daniel A. ; Rosas-Lemus, Monica ; Menzer, William M. ; Li, Chen ; Fang, Xuan ; Liang, Pingdong ; Tuz, Karina ; Minh, David D. L. ; Juárez, Oscar |
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Zeitschrift: | Journal of Biological Chemistry, Jg. 293 (2018-10-05), Heft 40, S. 15664-15677 |
Veröffentlichung: | 2018 |
Medientyp: | academicJournal |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.RA118.003194 |
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