2acz

File:2acz.gif

spinqualitylabelsall models 2acz, resolution 3.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Complex II (Succinate Dehydrogenase) From E. Coli with Atpenin A5 inhibitor co-crystallized at the ubiquinone binding site

OverviewOverview

The transfer of electrons and protons between membrane-bound respiratory, complexes is facilitated by lipid-soluble redox-active quinone molecules, (Q). This work presents a structural analysis of the quinone-binding site, (Q-site) identified in succinate:ubiquinone oxidoreductase (SQR) from, Escherichia coli. SQR, often referred to as Complex II or succinate, dehydrogenase, is a functional member of the Krebs cycle and the aerobic, respiratory chain and couples the oxidation of succinate to fumarate with, the reduction of quinone to quinol (QH(2)). The interaction between, ubiquinone and the Q-site of the protein appears to be mediated solely by, hydrogen bonding between the O1 carbonyl group of the quinone and the side, chain of a conserved tyrosine residue. In this work, SQR was, co-crystallized with the ubiquinone binding-site inhibitor Atpenin A5, (AA5) to confirm the binding position of the inhibitor and reveal, additional structural details of the Q-site. The electron density for AA5, was located within the same hydrophobic pocket as ubiquinone at, however, a different position within the pocket. AA5 was bound deeper into the site, prompting further assessment using protein-ligand docking experiments in, silico. The initial interpretation of the Q-site was re-evaluated in the, light of the new SQR-AA5 structure and protein-ligand docking data. Two, binding positions, the Q(1)-site and Q(2)-site, are proposed for the E., coli SQR quinone-binding site to explain these data. At the Q(2)-site, the, side chains of a serine and histidine residue are suitably positioned to, provide hydrogen bonding partners to the O4 carbonyl and methoxy groups of, ubiquinone, respectively. This allows us to propose a mechanism for the, reduction of ubiquinone during the catalytic turnover of the enzyme.

About this StructureAbout this Structure

2ACZ is a Protein complex structure of sequences from Escherichia coli with OAA, FAD, FES, SF4, F3S, HEB, AT5 and CDN as ligands. Active as Succinate dehydrogenase, with EC number 1.3.99.1 Full crystallographic information is available from OCA.

ReferenceReference

Structural and computational analysis of the quinone-binding site of complex II (succinate-ubiquinone oxidoreductase): a mechanism of electron transfer and proton conduction during ubiquinone reduction., Horsefield R, Yankovskaya V, Sexton G, Whittingham W, Shiomi K, Omura S, Byrne B, Cecchini G, Iwata S, J Biol Chem. 2006 Mar 17;281(11):7309-16. Epub 2005 Dec 27. PMID:16407191

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