PDBsum entry 2ad0

Oxidoreductase/electron transport

PDB id: 2ad0

Contents

Protein chains

588 a.a.

238 a.a.

129 a.a.

113 a.a.

Ligands

OAA

FAD

FES

FS4

F3S

HEM

CBE

CDN

Metals

_CA ×2

Waters ×140

Theoretical model

PDB id:

2ad0

Name:

Oxidoreductase/electron transport

Title:

Complex ii (succinate dehydrogenase) from e. Coli with carboxin inhibitor docked at the ubiquinone binding site

Structure:

Succinate dehydrogenase flavoprotein subunit. Chain: a. Succinate dehydrogenase iron-sulfur protein. Chain: b. Succinate dehydrogenase cytochrome b556 subunit. Chain: c. Synonym: cytochrome b-556. Succinate dehydrogenase hydrophobic membrane anchor protein.

Source:

Escherichia coli. Bacteria. Bacteria

Authors:

R.Horsefield,V.Yankovskaya,G.Sexton,W.Whittingham,K.Shiomi, S.Omura,B.Byrne,G.Cecchini,S.Iwata

Key ref:

R.Horsefield et al. (2006). 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. J Biol Chem, 281, 7309-7316. PubMed id: 16407191 DOI: 10.1074/jbc.M508173200

Date:

19-Jul-05 Release date: 03-Jan-06

Protein chain

P10444  (DHSA_ECOLI) -

Protein chain

P07014  (SDHB_ECOLI) -  Succinate dehydrogenase iron-sulfur subunit from Escherichia coli (strain K12)

Seq: 238 a.a.

Struc: 238 a.a.

Protein chain

P69054  (DHSC_ECOLI) -  Succinate dehydrogenase cytochrome b556 subunit from Escherichia coli (strain K12)

Seq: 129 a.a.

Struc: 129 a.a.

Protein chain

P10445  (DHSD_ECOLI) -

Enzyme reactions

• Enzyme class: Chains A, B: E.C.1.3.99.1 - Deleted entry.
• Reaction: Succinate + acceptor = fumarate + reduced acceptor

Succinate (Bound ligand (Het Group name = OAA) matches with 8889.00% similarity corresponds exactly) + acceptor = fumarate + reduced acceptor

• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) matches with 41.33% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M508173200

J Biol Chem 281:7309-7316 (2006)

PubMed id: 16407191

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.

R.Horsefield, V.Yankovskaya, G.Sexton, W.Whittingham, K.Shiomi, S.Omura, B.Byrne, G.Cecchini, S.Iwata.

ABSTRACT

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.

Selected figure(s)

Figure 1.
FIGURE 1. Q-site in E. coli SQR; slab view with the surface and interior of the protein shown in beige and gray, respectively. Binding positions at the Q[1]-site for ubiquinone in the native structure (blue, PDB 1NEK [PDB] ) (A) and DNP17 inhibitor (orange, PDB 1NEN) (B) and the Q[2]-site for GOLD docked ubiquinone (green) (C) and carboxin inhibitor (Cbx, purple, PDB 2AD0) (D). Key residues (gray) are labeled, and protein-ligand interactions shown by red dotted lines with the distances labeled.

Figure 4.
FIGURE 4. Putative proton transfer pathway in E. coli SQR. A, surface representation of the trimer with the opening of the pathway to the cytoplasm viewed parallel to the membrane and B, slab view from the cytoplasm along the membrane normal showing the path of the chain from one side of the anchor monomer to the Q-site on the other. The surface of the protein (beige), water molecules (red space-fill), and ubiquinone (blue space-fill) are shown. C, detailed view of the pathway from the cytoplasm (red) to the Q-site (blue/green) in E. coli SQR; water molecules (red space-fill) and conserved residue side chains (gray) interacting with the pathway are shown. Ubiquinone (Q[1]-site, blue) and AA5 (Q[2]-site, green) at the Q-site are labeled accordingly. Hydrogen bonds and other distances are shown by red and gray dotted lines, respectively, and the distances are labeled.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 7309-7316) copyright 2006.

Figures were selected by the author.