6saq
From Proteopedia
wild-type NuoEF from Aquifex aeolicus bound to NADH-OH
Structural highlights
FunctionNUOE_AQUAE NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient (By similarity). Publication Abstract from PubMedNADH: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 A 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. Structural Basis for Inhibition of ROS-Producing Respiratory Complex I by NADH-OH.,Vranas M, Wohlwend D, Qiu D, Gerhardt S, Trncik C, Pervaiz M, Ritter K, Steimle S, Randazzo A, Einsle O, Gunther S, Jessen HJ, Kotlyar A, Friedrich T Angew Chem Int Ed Engl. 2021 Dec 20;60(52):27277-27281. doi: , 10.1002/anie.202112165. Epub 2021 Nov 15. PMID:34612584[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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