6SAQ

wild-type NuoEF from Aquifex aeolicus bound to NADH-OH

Summary for 6SAQ

• Entry DOI: 10.2210/pdb6saq/pdb
• Descriptor: NADH-quinone oxidoreductase subunit E, NADH-quinone oxidoreductase subunit F, FE2/S2 (INORGANIC) CLUSTER, ... (8 entities in total)
• Functional Keywords: nadh:ubiquinone oxidoreductase, complex i, electron transport
• Biological source: Aquifex aeolicus (strain VF5); More
• Total number of polymer chains: 4
• Total formula weight: 138200.99

Authors

Gerhardt, S. (deposition date: 2019-07-17, release date: 2020-07-22, Last modification date: 2024-01-24)

Primary citation

Friedrich, T.,Vranas, M.,Wohlwend, D.,Qiu, D.,Gerhardt, S.,Trncik, C.,Pervaiz, M.,Ritter, K.,Steimle, S.,Randazzo, A.,Einsle, O.,Gunther, S.,Jessen, H.J.,Kotlyar, A.
Structural Basis for Inhibition of ROS-Producing Respiratory Complex I by NADH-OH.
Angew.Chem.Int.Ed.Engl., 2021

PubMed Abstract: NADH:ubiquinone oxidoreductase, respiratory complex I, plays a central role in cellular energy metabolism. As a major source of reactive oxygen species (ROS) it affects ageing and mitochondrial dysfunction. The novel inhibitor NADH-OH specifically blocks NADH oxidation and ROS production by complex I in nanomolar concentrations. Attempts to elucidate its structure by NMR spectroscopy have failed. Here, by using X-ray crystallographic analysis, we report the structure of NADH-OH bound in the active site of a soluble fragment of complex I at 2.0 Å resolution. We have identified key amino acid residues that are specific and essential for binding NADH-OH. Furthermore, the structure sheds light on the specificity of NADH-OH towards the unique Rossmann-fold of complex I and indicates a regulatory role in mitochondrial ROS generation. In addition, NADH-OH acts as a lead-structure for the synthesis of a novel class of ROS suppressors.

PubMed: 34612584
DOI: 10.1002/anie.202112165

Experimental method

X-RAY DIFFRACTION (2.02 Å)