@article{1980, 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.}, author = {Heikal, Adam and Nakatani, Yoshio and Dunn, Elyse A and Weimar, Marion R and Day, Catherine and Baker, Edward N and Lott, Shaun J and Leonid Sazanov and Cook, Gregory}, journal = {Molecular Microbiology}, number = {5}, pages = {950 -- 964}, publisher = {Wiley-Blackwell}, title = {{Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation}}, doi = {10.1111/mmi.12507}, volume = {91}, year = {2014}, }