Model of Fumarate Reductase dimer - (scroll down for tutorial buttons)

Reload dimer as backbone model.
Reload monomer as backbone model.
Note: some of the views will be easier to locate if you use the monomer model

Introduction

See notes on succinate:fumarate oxidoreductase for an introduction to Complex II of the respiratory chain. The fumarate reductase is a closely related enzyme that normally functions in the reverse direction, using menaquinol from the membrane to reduce fumarate to succinate.
In the initial view, the dimeric complex is shown as a ribbon model colored by chain, with prosthetic groups as ball and stick models, except for iron sulfur clusters, shown as spacefilling atoms. The complex is shown vertical with respect to the membrane plane, with the P-phase (bacterial periplasm, mitochondrial inter-membrane space) at botton, N-phase (bacterial cytplasm, mitochondrial matrix) at top. One monomer (chains A, B, C and D) is colored dark through pale blue, the second (chains M, N, O and P) is colored green blue through green.
(To stop or start rotation, click on image with right mouse button, and select Rotation.)

Reset view of the protein as a backbone model. Spacefill Chain A, Chain B, Chain C, Chain D.

The protein is color-coded to show structure; helices are pink, coils white, sheets orange. The prosthetic groups are shown as spacefilling models colored by chain. The trans-membrane helices in the membrane spanning segments (chains C,D and O,P) are obvious in the lower half of the structure.

Prosthetic groups in CPK.

Show liganding of OAA. The binding site for OAA (as a competitive inhibitor at the substrate binding site) includes the FAD prosthetic group, which (in one monomer) provides H-bonds to oxygens of the two carboxylates from the flavin ring N-atoms. The sites are in chains A and M of the two monomers. Only A is shown.

Show liganding of FAD. The sites are in chains A and M of the two monomers. Only A is shown.

The protein environment of the N-side menaquinone. Hydrophobic residues are in white, polar in green, acidic in red, and basic in blue. Note the predominantly strongly polar environment, and the paucity of hydrophobic side chains. The latter are provided by aromats tryptophan (moderately polar), and phenylalanine.

Show liganding of N-side menaquinone. The site is contibuted by chains B, C and D of one monomer, N, O and P of the other. Only site in B, C, D is shown. The "classical" quinone ligands (His, Ser) do not appear to serve this function at this site. The strong polarity, and the neighboring Lys (possible ligand), His and Arg residues would likely stabilize the semiquinone anion.

The protein environment of the P-side menaquinone. Note the predominantly hydrophobic side chains, and lack of polarity.

Show liganding of P-side menaquinone. The site is contibuted by chains C and D of one monomer, O and P of the other. Only site in C, D is shown. Note the absence of polar ligands to the quinone carbonyl oxygens. Binding appears to be predominantly through hydrophobic packing.

Show the chain of iron sulfur centers connecting the substrate and menaquinone binding sites. Note that (in order from the FAD end) we have a [2Fe-2S] center, a [4Fe-4S] center, and a [3Fe-4S] center, the latter with inly 3 liganding cysteines. From the distances between centers, it appears likely that all the clusters are in the electron transfer path, despite the wide range of Em values.

©Copyright 1996-2000, Antony Crofts, University of Illinois at Urbana-Champaign, a-crofts@uiuc.edu