8e9g | pdb_00008e9g

Mycobacterial respiratory complex I with both quinone positions modelled

spinqualitylabelsall models 8e9g, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8e9g is a 10 chain structure with sequence from Mycolicibacterium smegmatis MC2 155. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FES, FMN, GTP, MQ9, SF4, XP2, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0QU37_MYCS2 Publication Abstract from PubMed Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by Mycobacterium tuberculosis and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of Mycobacterium smegmatis in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the "orphan" two-component response regulator protein MSMEG_2064 as a subunit of the assembly. MSMEG_2064 in the complex occupies a site similar to the proposed redox-sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel, comparable to ubiquinone in other structures and suggesting a conserved quinone binding mechanism. Structure of mycobacterial respiratory complex I.,Liang Y, Plourde A, Bueler SA, Liu J, Brzezinski P, Vahidi S, Rubinstein JL Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2214949120. doi: , 10.1073/pnas.2214949120. Epub 2023 Mar 23. PMID:36952383 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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