---
OA_type: free access
_id: '1980'
abstract:
- lang: eng
  text: 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.
acknowledgement: Funded by      Health Research Council of New Zealand     Royal Society
  of New Zealand     University of Otago     New Zealand Synchrotron Group
article_processing_charge: No
article_type: original
author:
- first_name: Adam
  full_name: Heikal, Adam
  last_name: Heikal
- first_name: Yoshio
  full_name: Nakatani, Yoshio
  last_name: Nakatani
- first_name: Elyse
  full_name: Dunn, Elyse
  last_name: Dunn
- first_name: Marion
  full_name: Weimar, Marion
  last_name: Weimar
- first_name: Catherine
  full_name: Day, Catherine
  last_name: Day
- first_name: Edward
  full_name: Baker, Edward
  last_name: Baker
- first_name: Shaun
  full_name: Lott, Shaun
  last_name: Lott
- first_name: Leonid A
  full_name: Sazanov, Leonid A
  id: 338D39FE-F248-11E8-B48F-1D18A9856A87
  last_name: Sazanov
  orcid: 0000-0002-0977-7989
- first_name: Gregory
  full_name: Cook, Gregory
  last_name: Cook
citation:
  ama: '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.
    <i>Molecular Microbiology</i>. 2014;91(5):950-964. doi:<a href="https://doi.org/10.1111/mmi.12507">10.1111/mmi.12507</a>'
  apa: '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. <i>Molecular Microbiology</i>.
    Wiley-Blackwell. <a href="https://doi.org/10.1111/mmi.12507">https://doi.org/10.1111/mmi.12507</a>'
  chicago: '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.” <i>Molecular Microbiology</i>. Wiley-Blackwell, 2014.
    <a href="https://doi.org/10.1111/mmi.12507">https://doi.org/10.1111/mmi.12507</a>.'
  ieee: 'A. Heikal <i>et al.</i>, “Structure of the bacterial type II NADH dehydrogenase:
    a monotopic membrane protein with an essential role in energy generation,” <i>Molecular
    Microbiology</i>, vol. 91, no. 5. Wiley-Blackwell, pp. 950–964, 2014.'
  ista: '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.'
  mla: 'Heikal, Adam, et al. “Structure of the Bacterial Type II NADH Dehydrogenase:
    A Monotopic Membrane Protein with an Essential Role in Energy Generation.” <i>Molecular
    Microbiology</i>, vol. 91, no. 5, Wiley-Blackwell, 2014, pp. 950–64, doi:<a href="https://doi.org/10.1111/mmi.12507">10.1111/mmi.12507</a>.'
  short: 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.
date_created: 2018-12-11T11:55:01Z
date_published: 2014-03-01T00:00:00Z
date_updated: 2026-09-04T11:27:46Z
day: '01'
doi: 10.1111/mmi.12507
extern: '1'
external_id:
  pmid:
  - '24444429'
intvolume: '        91'
issue: '5'
language:
- iso: eng
month: '03'
oa_version: None
page: 950 - 964
pmid: 1
publication: Molecular Microbiology
publication_identifier:
  eissn:
  - 1365-2958
  issn:
  - 0950-382X
publication_status: published
publisher: Wiley-Blackwell
publist_id: '5103'
status: public
title: 'Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane
  protein with an essential role in energy generation'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 91
year: '2014'
...