PDBsum entry 1orz

Oxidoreductase

PDB id: 1orz

Contents

Protein chains

612 a.a.

246 a.a.

148 a.a.

150 a.a.

Theoretical model

PDB id:

1orz

Name:

Oxidoreductase

Title:

Three-dimensional model of the saccharomyces cerevisiae succinate dehydrogenase

Structure:

Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial. Chain: a. Synonym: fp, flavoprotein subunit of complex ii, sdh1p. Succinate dehydrogenase [ubiquinone] iron-sulfur protein, mitochondrial. Chain: b. Synonym: ip, sdh2p. Succinate dehydrogenase cytochrome b subunit,

Source:

Saccharomyces cerevisiae. Yeast. Yeast

Authors:

K.S.Oyedotun,B.D.Lemire

Key ref:

K.S.Oyedotun and B.D.Lemire (2004). The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase. Homology modeling, cofactor docking, and molecular dynamics simulation studies. J Biol Chem, 279, 9424-9431. PubMed id: 14672929 DOI: 10.1074/jbc.M311876200

Date:

17-Mar-03 Release date: 09-Mar-04

Protein chain

Q00711  (DHSA_YEAST) -  Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial

Seq: 640 a.a.

Struc: 612 a.a.

Protein chain

P21801  (DHSB_YEAST) -  Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial

Seq: 266 a.a.

Struc: 246 a.a.

Protein chain

P33421  (SDH3_YEAST) -  Succinate dehydrogenase [ubiquinone] cytochrome b subunit, mitochondrial

Seq: 198 a.a.

Struc: 148 a.a.

Protein chain

P37298  (DHSD_YEAST) -  Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial

Seq: 181 a.a.

Struc: 150 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.1.3.5.1 - succinate dehydrogenase.
• Pathway: Citric acid cycle
• Reaction: a quinone + succinate = fumarate + a quinol
• Cofactor: FAD; Iron-sulfur

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

reference

DOI no: 10.1074/jbc.M311876200

J Biol Chem 279:9424-9431 (2004)

PubMed id: 14672929

The quaternary structure of the Saccharomyces cerevisiae succinate dehydrogenase. Homology modeling, cofactor docking, and molecular dynamics simulation studies.

K.S.Oyedotun, B.D.Lemire.

ABSTRACT

Succinate dehydrogenases and fumarate reductases are complex mitochondrial or bacterial respiratory chain proteins with remarkably similar structures and functions. Succinate dehydrogenase oxidizes succinate and reduces ubiquinone using a flavin adenine dinucleotide cofactor and iron-sulfur clusters to transport electrons. A model of the quaternary structure of the tetrameric Saccharomyces cerevisiae succinate dehydrogenase was constructed based on the crystal structures of the Escherichia coli succinate dehydrogenase, the E. coli fumarate reductase, and the Wolinella succinogenes fumarate reductase. One FAD and three iron-sulfur clusters were docked into the Sdh1p and Sdh2p catalytic dimer. One b-type heme and two ubiquinone or inhibitor analog molecules were docked into the Sdh3p and Sdh4p membrane dimer. The model is consistent with numerous experimental observations. The calculated free energies of inhibitor binding are in excellent agreement with the experimentally determined inhibitory constants. Functionally important residues identified by mutagenesis of the SDH3 and SDH4 genes are located near the two proposed quinone-binding sites, which are separated by the heme. The proximal quinone-binding site, located nearest the catalytic dimer, has a considerably more polar environment than the distal site. Alternative low energy conformations of the membrane subunits were explored in a molecular dynamics simulation of the dimer embedded in a phospholipid bilayer. The simulation offers insight into why Sdh4p Cys-78 may be serving as the second axial ligand for the heme instead of a histidine residue. We discuss the possible roles of heme and of the two quinone-binding sites in electron transport.

Selected figure(s)

Figure 2.
FIG. 2. Quaternary structure model of the S. cerevisiae SDH. A, ribbon representation of SDH. Sdh1p, Sdh2p, Sdh3p, and Sdh4p are shown in gold, green, red, and blue, respectively. The iron-sulfur clusters are shown as cyan (S atoms) and red (Fe atoms); FAD and heme b are shown as purple; quinones are shown in yellow. B, superposition of the S. cerevisiae SDH (blue) with the E. coli SDH (yellow). C, structure of the flavoprotein (Sdh1p). His-62, which is covalently linked to the FAD is shown in red. D, the iron-sulfur protein (Sdh2p) with the three iron-sulfur clusters.

Figure 7.
FIG. 7. A, averaged structure of the Sdh2p-Sdh3p-Sdh4p trimer calculated after MD simulation and the pathway of electron transfer. A, superimposition of the SDH trimer structure after molecular dynamics (blue) with the starting conformation (yellow). Sdh4p residues that are most mobile during molecular dynamics simulation are colored red. The average structure was calculated from the equilibrium ensemble of the last 500 ps using the g_rmsf utility of GROMACS. B, structure of the heme-binding site after a 5-ns molecular dynamics simulation. C, cofactor location and pathway of electron transfer. Edge-to-edge distances (Å) between the cofactors are indicated.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 9424-9431) copyright 2004.

Figures were selected by an automated process.