2acz
From Proteopedia
(New page: 200px<br /><applet load="2acz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2acz, resolution 3.1Å" /> '''Complex II (Succinate...) |
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| - | [[Image:2acz.gif|left|200px]]<br /><applet load="2acz" size=" | + | [[Image:2acz.gif|left|200px]]<br /><applet load="2acz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2acz, resolution 3.1Å" /> | caption="2acz, resolution 3.1Å" /> | ||
'''Complex II (Succinate Dehydrogenase) From E. Coli with Atpenin A5 inhibitor co-crystallized at the ubiquinone binding site'''<br /> | '''Complex II (Succinate Dehydrogenase) From E. Coli with Atpenin A5 inhibitor co-crystallized at the ubiquinone binding site'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The transfer of electrons and protons between membrane-bound respiratory | + | 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 Structure== | ==About this Structure== | ||
| - | 2ACZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with OAA, FAD, FES, SF4, F3S, HEB, AT5 and CDN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Succinate_dehydrogenase Succinate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.1 1.3.99.1] Full crystallographic information is available from [http:// | + | 2ACZ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=OAA:'>OAA</scene>, <scene name='pdbligand=FAD:'>FAD</scene>, <scene name='pdbligand=FES:'>FES</scene>, <scene name='pdbligand=SF4:'>SF4</scene>, <scene name='pdbligand=F3S:'>F3S</scene>, <scene name='pdbligand=HEB:'>HEB</scene>, <scene name='pdbligand=AT5:'>AT5</scene> and <scene name='pdbligand=CDN:'>CDN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Succinate_dehydrogenase Succinate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.99.1 1.3.99.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ACZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: succinate:ubiquinone oxidoreductase]] | [[Category: succinate:ubiquinone oxidoreductase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:13 2008'' |
Revision as of 14:26, 21 February 2008
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Complex II (Succinate Dehydrogenase) From E. Coli with Atpenin A5 inhibitor co-crystallized at the ubiquinone binding site
Overview
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 Structure
2ACZ is a Protein complex structure of sequences from Escherichia coli with , , , , , , and as ligands. Active as Succinate dehydrogenase, with EC number 1.3.99.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:26:13 2008
Categories: Escherichia coli | Protein complex | Succinate dehydrogenase | Byrne, B. | Cecchini, G. | Horsefield, R. | Iwata, S. | Omura, S. | Sexton, G. | Shiomi, K. | Whittingham, W. | Yankovskaya, V. | AT5 | CDN | F3S | FAD | FES | HEB | OAA | SF4 | Aa5 | Aerobic reparatory complex ii | At5 | Atpenin a5 | Membrane protein | Sdh | Sqr | Succinate:ubiquinone oxidoreductase
