Structural highlights
7xk3 is a 6 chain structure with sequence from Vibrio cholerae O395. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NQRA_VIBC3] NQR complex catalyzes the reduction of ubiquinone-1 to ubiquinol by two successive reactions, coupled with the transport of Na(+) ions from the cytoplasm to the periplasm. NqrA to NqrE are probably involved in the second step, the conversion of ubisemiquinone to ubiquinol.[HAMAP-Rule:MF_00425]
Publication Abstract from PubMed
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-A 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.
Cryo-EM structures of Na(+)-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae.,Kishikawa JI, Ishikawa M, Masuya T, Murai M, Kitazumi Y, Butler NL, Kato T, Barquera B, Miyoshi H Nat Commun. 2022 Jul 26;13(1):4082. doi: 10.1038/s41467-022-31718-1. PMID:35882843[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kishikawa JI, Ishikawa M, Masuya T, Murai M, Kitazumi Y, Butler NL, Kato T, Barquera B, Miyoshi H. Cryo-EM structures of Na(+)-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae. Nat Commun. 2022 Jul 26;13(1):4082. doi: 10.1038/s41467-022-31718-1. PMID:35882843 doi:http://dx.doi.org/10.1038/s41467-022-31718-1
