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Title | Cryo-EM structures of Na-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae. |
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Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 4082, Year 2022 |
Publish date | Jul 26, 2022 |
Authors | Jun-Ichi Kishikawa / Moe Ishikawa / Takahiro Masuya / Masatoshi Murai / Yuki Kitazumi / Nicole L Butler / Takayuki Kato / Blanca Barquera / Hideto Miyoshi / |
PubMed Abstract | The Na-pumping NADH-ubiquinone oxidoreductase (Na-NQR) couples electron transfer from NADH to ubiquinone with Na-pumping, generating an electrochemical Na gradient that is essential for energy- ...The Na-pumping NADH-ubiquinone oxidoreductase (Na-NQR) couples electron transfer from NADH to ubiquinone with Na-pumping, generating an electrochemical Na gradient that is essential for energy-consuming reactions in bacteria. Since Na-NQR is exclusively found in prokaryotes, it is a promising target for highly selective antibiotics. However, the molecular mechanism of inhibition is not well-understood for lack of the atomic structural information about an inhibitor-bound state. Here we present cryo-electron microscopy structures of Na-NQR from Vibrio cholerae with or without a bound inhibitor at 2.5- to 3.1-Å resolution. The structures reveal the arrangement of all six redox cofactors including a herein identified 2Fe-2S cluster located between the NqrD and NqrE subunits. A large part of the hydrophilic NqrF is barely visible in the density map, suggesting a high degree of flexibility. This flexibility may be responsible to reducing the long distance between the 2Fe-2S centers in NqrF and NqrD/E. Two different types of specific inhibitors bind to the N-terminal region of NqrB, which is disordered in the absence of inhibitors. The present study provides a foundation for understanding the function of Na-NQR and the binding manner of specific inhibitors. |
External links | Nat Commun / PubMed:35882843 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 3.1 Å |
Structure data | EMDB-33242, PDB-7xk3: EMDB-33243, PDB-7xk4: EMDB-33244, PDB-7xk5: EMDB-33245, PDB-7xk6: EMDB-33246, PDB-7xk7: |
Chemicals | ChemComp-FMN: ChemComp-RBF: ChemComp-PEE: ChemComp-LMT: ChemComp-FES: ChemComp-CA: ChemComp-FAD: ChemComp-0NI: ChemComp-HOH: ChemComp-IQT: |
Source |
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Keywords | TRANSLOCASE / NADH-quinone oxidoreductase / redox-driven sodium pump / bioenergetics / Vibrio cholerae / electron transport / membrane protein complex / OXIDOREDUCTASE |