Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation

A. Heikal, Y. Nakatani, E. Dunn, M. Weimar, C. Day, E. Baker, S. Lott, L.A. Sazanov, G. Cook, Molecular Microbiology 91 (2014) 950–964.

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Journal Article | Published
Author
Heikal, Adam ; Nakatani, Yoshio; Dunn, Elyse A; Weimar, Marion R; Day, Catherine; Baker, Edward N; Lott, Shaun J; Sazanov, Leonid AIST Austria ; Cook, Gregory
Abstract
Non-proton pumping type II NADH dehydrogenase (NDH-2) plays a central role in the respiratory metabolism of bacteria, and in the mitochondria of fungi, plants and protists. The lack of NDH-2 in mammalian mitochondria and its essentiality in important bacterial pathogens suggests these enzymes may represent a potential new drug target to combat microbial pathogens. Here, we report the first crystal structure of a bacterial NDH-2 enzyme at 2.5Å resolution from Caldalkalibacillus thermarum. The NDH-2 structure reveals a homodimeric organization that has a unique dimer interface. NDH-2 is localized to the cytoplasmic membrane by two separated C-terminal membrane-anchoring regions that are essential for membrane localization and FAD binding, but not NDH-2 dimerization. Comparison of bacterial NDH-2 with the yeast NADH dehydrogenase (Ndi1) structure revealed non-overlapping binding sites for quinone and NADH in the bacterial enzyme. The bacterial NDH-2 structure establishes a framework for the structure-based design of small-molecule inhibitors.
Publishing Year
Date Published
2014-03-01
Journal Title
Molecular Microbiology
Acknowledgement
Funded by Health Research Council of New Zealand Royal Society of New Zealand University of Otago New Zealand Synchrotron Group
Volume
91
Issue
5
Page
950 - 964
IST-REx-ID

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Heikal A, Nakatani Y, Dunn E, et al. Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation. Molecular Microbiology. 2014;91(5):950-964. doi:10.1111/mmi.12507
Heikal, A., Nakatani, Y., Dunn, E., Weimar, M., Day, C., Baker, E., … Cook, G. (2014). Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation. Molecular Microbiology, 91(5), 950–964. https://doi.org/10.1111/mmi.12507
Heikal, Adam, Yoshio Nakatani, Elyse Dunn, Marion Weimar, Catherine Day, Edward Baker, Shaun Lott, Leonid A Sazanov, and Gregory Cook. “Structure of the Bacterial Type II NADH Dehydrogenase: A Monotopic Membrane Protein with an Essential Role in Energy Generation.” Molecular Microbiology 91, no. 5 (2014): 950–64. https://doi.org/10.1111/mmi.12507.
A. Heikal et al., “Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation,” Molecular Microbiology, vol. 91, no. 5, pp. 950–964, 2014.
Heikal A, Nakatani Y, Dunn E, Weimar M, Day C, Baker E, Lott S, Sazanov LA, Cook G. 2014. Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation. Molecular Microbiology. 91(5), 950–964.
Heikal, Adam, et al. “Structure of the Bacterial Type II NADH Dehydrogenase: A Monotopic Membrane Protein with an Essential Role in Energy Generation.” Molecular Microbiology, vol. 91, no. 5, Wiley-Blackwell, 2014, pp. 950–64, doi:10.1111/mmi.12507.

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