7xk3
Cryo-EM structure of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae, state 1Cryo-EM structure of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae, state 1
Structural highlights
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 PubMedThe 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
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