6ztq

Cryo-EM structure of respiratory complex I from Mus musculus inhibited by piericidin A at 3.0 A

spinqualitylabelsall models 6ztq, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ztq is a 10 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: 2MR, 3PE, AME, ATP, AYA, CDL, EHZ, FES, FME, FMN, HQH, NDP, PC1, SAC, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NU2M_MOUSE Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). Publication Abstract from PubMed Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-A resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I. Structure of inhibitor-bound mammalian complex I.,Bridges HR, Fedor JG, Blaza JN, Di Luca A, Jussupow A, Jarman OD, Wright JJ, Agip AA, Gamiz-Hernandez AP, Roessler MM, Kaila VRI, Hirst J Nat Commun. 2020 Oct 16;11(1):5261. doi: 10.1038/s41467-020-18950-3. PMID:33067417 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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