Ubiquinone:cytochrome structure

Complex III Ubiquinone to Cytochrome c The next respiratory complex. Complex III, also called cytochrome bci complex or ubiquinone cytochrome c oxidoreductase, couples the transfer of electrons from ubiquinol (QH2) to cytochrome c with the vectorial transport of protons from the matrix to the intermembrane space. The determination of the complete structure of this huge complex (Fig. 19-11) and of Complex IV (below) by x-ray crystallography, achieved between 1995 and 1998, were landmarks in the study of mitochondrial electron transfer, providing the structural framework to integrate the many biochemical observations on the functions of the respiratory complexes. 

Ubiquinone or Q (coenjyme Q) (Figure 12-5) finks the flavoproteins to cytochrome h, the member of the cytochrome chain of lowest redox potential. Q exists in the oxidized quinone or reduced quinol form under aerobic or anaerobic conditions, respectively. The structure of Q is very similar to that of vitamin K and vitamin E (Chapter 45) and of plastoquinone, found in chloroplasts. Q acts as a mobile component of the respiratory chain that collects reducing equivalents from the more fixed flavoprotein complexes and passes them on to the cytochromes. 

In 2003, the Di Xia group published an X-ray crystallographic study of substrate and inhibitor molecules at the Qo and Qi site. They intended to compare the structure of the native enzyme (PDB INTM) with the cytochrome bci complex having substrate or inhibitors in the Qo and/or Qi sites. The complex with substrate ubiquinone UQ2 (PDB INTZ) was discussed previously in this section. The complex with the inhibitor antimycin Ai (PDB INTK) will be discussed here. A fourth complex with the ubiquinone-model... 

In 2005, the E. A. Berry group published X-ray crystallographic studies of cytochrome bci with bound inhibitors. The structure of PDB 1PP9, resolution 2.23 A, includes stigmatellin A (SMA) in the Qo site and substrate ubiquinone (UQ) in the Qi site, while PDB IPPJ, resolution 2.28 A, includes stigmatellin A in the Qo site and antimycin Ai (ANY) in the Qi site. These... 

Ubiquinone is readily reduced to ubiquinol, a process requiring two protons and two electrons similarly, ubiquinol is readily oxidized back to ubiquinone. This redox process is important in oxidative phosphorylation, in that it links hydrogen transfer to electron transfer. The cytochromes are haem-containing proteins (see Box 11.4). As we have seen, haem is an iron-porphyrin complex. Alternate oxidation-reduction of the iron between Fe + (reduced form) and Fe + (oxidized form) in the various cytochromes is responsible for the latter part of the electron transport chain. The individual cytochromes vary structurally, and their classification... 

FIGURE 19-11 Cytochrome be, complex (Complex III). The complex is a dimer of identical monomers, each with 11 different subunits. (a) Structure of a monomer. The functional core is three subunits cytochrome b (green) with its two hemes (bH and foL, light red) the Rieske iron-sulfur protein (purple) with its 2Fe-2S centers (yellow) and cytochrome ci (blue) with its heme (red) (PDB ID 1BGY). (b) The dimeric functional unit. Cytochrome c, and the Rieske iron-sulfur protein project from the P surface and can interact with cytochrome c (not part of the functional complex) in the intermembrane space. The complex has two distinct binding sites for ubiquinone, QN and QP, which correspond to the sites of inhibition by two drugs that block oxidative phosphorylation. Antimycin A, which blocks electron flow from heme bH to Q, binds at QN, close to heme bH on the N (matrix) side of the membrane. Myxothiazol, which prevents electron flow from... 

We now recognize not only that these complexes are discrete structural units but also that they are functional units. Complete X-ray crystallographic structures are available for complexes III and IV and for much of the ATP synthase complex. As is indicated in Fig. 18-5, complexes I - IV are linked by two soluble electron carriers, ubiquinone and cytochrome c. 

Cytochrome cdj needs three things to reduee nitrite to nitric oxide, substrates nitrite and protons plus eleetrons. The first two are simply supplied from the environment but where do the eleetrons eome from Cytochrome cdi derives its electrons from the eleetron transport system in the cytoplasmic membranes of baeteria. Thus, for example, eleetrons ean originate from NADH and pass via NADH dehydrogenase, ubiquinone/ubiquinol and the cytochrome bc eomplex to nitrite reduetase (Berks et al., 1995 Zumft, 1997). It is known that the eytoehrome bc eomplex is used beeause electron transfer from physiologieal donors, e.g. NADH, to nitrite reduetase is blocked by specific inhibitors, e.g. myxothiazol, of this complex. An important issue arises when we eonsider how electrons are transferred from the cytochrome fccj complex to eytoehrome cd, which, recall, is a water-soluble protein located in the periplasm. The structure of the cytochrome be I complex (determined for the mitoehondrial protein but we can assume that the bacterial counterparts are similarly organised) shows that the... 

Weiss, H., and Leonard, K., 1987, Structure and function of mitochondrial ubiquinol cytochrome c reductase and NADH ubiquinone reductase, Chemica Scripta 27B 73n 81. 

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