| Title |
Structure of the bacterial type II NADH dehydrogenase: a monotopic membrane protein with an essential role in energy generation
|
|---|---|
| Published in |
Molecular Microbiology, January 2014
|
| DOI | 10.1111/mmi.12507 |
| Pubmed ID | |
| Authors | |
| 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. |
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Demographic breakdown
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Mendeley demographics
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Demographic breakdown
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| Student > Master | 33 | 17% |
| Researcher | 19 | 10% |
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| Student > Doctoral Student | 11 | 6% |
| Other | 27 | 14% |
| Unknown | 46 | 24% |
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| Other | 12 | 6% |
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