4NWZ

Structure of bacterial type II NADH dehydrogenase from Caldalkalibacillus thermarum at 2.5A resolution

Summary for 4NWZ

• Entry DOI: 10.2210/pdb4nwz/pdb
• Descriptor: FAD-dependent pyridine nucleotide-disulfide oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: rossmann fold, dehydrogenase, nucleotide binding, membrane/cytoplasm, oxidoreductase
• Biological source: Caldalkalibacillus thermarum
• Total number of polymer chains: 4
• Total formula weight: 181430.15

Authors

Nakatani, Y.,Heikal, A.,Lott, J.S.,Sazanov, L.A.,Baker, E.N.,Cook, G.M. (deposition date: 2013-12-07, release date: 2014-02-19, Last modification date: 2023-11-08)

Primary citation

Heikal, A.,Nakatani, Y.,Dunn, E.,Weimar, M.R.,Day, C.L.,Baker, E.N.,Lott, J.S.,Sazanov, L.A.,Cook, G.M.
Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation.
Mol.Microbiol., 91:950-964, 2014

PubMed 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 2.5 Å 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.

PubMed: 24444429
DOI: 10.1111/mmi.12507

Experimental method

X-RAY DIFFRACTION (2.5 Å)