Overview for MACiE Entry M0208
EC Number: 220.127.116.11 (A member of the Oxidoreductases, Acting on diphenols and related substances as donors, With a cytochrome as acceptor)
Enzyme Name: ubiquinol-cytochrome-c reductase
Biological Species: Saccharomyces cerevisiae (Baker's yeast)
Catalytic Chain UniprotKB Accession Codes:
- P08067 - Cytochrome b-c1 complex subunit Rieske, mitochondrial
- P07143 - Cytochrome c1, heme protein, mitochondrial
- P00163 - Cytochrome b
Representative PDB Code: 1ezv - STRUCTURE OF THE YEAST CYTOCHROME BC1 COMPLEX CO-CRYSTALLIZED WITH AN ANTIBODY FV-FRAGMENT (Resolution = 2.30 Å).
Catalytic CATH Codes:
"Other" CATH Codes:
- 1.10.760.10 - Cytochrome c
- 18.104.22.168 - Immunoglobulins
- 3.30.830.10 - Cytochrome Bc1 Complex; Chain A, domain 1
- 22.214.171.124 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
- 1.10.1090.10 - Cytochrome Bc1 Complex; Chain F
- 126.96.36.199 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
- 1.10.287.20 - Helix Hairpins
- 188.8.131.520 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
- 184.108.40.2060 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
Display structure information
This reaction is irreversible.
Overall Comment: Ubiquinol-cytochrome c reductase is a redox driven proton pump that utilises the free energy of ubiquinol reduction for the creation of a proton gradient across membranes (periplasma in prokaryotes and intermembrane space in mitochondria) membrane. The proton-motive Q cycle mechanism best explains experimental results on the ET pathway through the four redox centres of the bc1 complex. The mechanism postulates two separate quinone binding sites, one for quinol oxidation (Qo site) and the other for quinone reduction (Qi site), and a bifurcated electron flow at the Qo site where the first electron from the the substrate quinol is transferred sequentially to the ISP domain (containing an iron-sulfur complex) to the cyt. c1 domain (containing a 1c type heme), and eventually to the soluble electron acceptor cyt. c, whereas the second electron is transferred to the b-type hemes bL and bH in sequence, ending at a quinone or a semiquinone anion at the Qi site. The complete Q cycle consumes two molecules of quinol, generates one molecule of quinone and translocates four protons to the positive side of the membrane. The exact order of the steps in this mechanism remains unclear. There is evidence of a long range interaction between both catalytic sites. Although it is not entirely clear is the oxidation/reduction of the quinol/quinone species are concerted or stepwise, evidence supports the stepwise manner shown here. It has been documented  that the ubisemiquinone radical produced during this step required an alkaline pH to be stable in the Qi site, consistent with the assumption that both Asp228 and His201 are deprotonated. Furthermore, electron nuclear double resonance experiments showed exchangeable H-bonds bonds to the ubisemiquinone radical, suggesting that the water-mediated H-bonding acts to stabilise the free radical formed.
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Stepwise Description of the Reaction
|Step 1||Glu272 deprotonates the quinol substrate. His161 (bound to a Rieske iron-sulfur cluster) deprotonates the second alcohol group. This initiates a single electron transfer to the Rieske iron-sulfur cluster forming the semi-quinone intermediate.|
|Step 2||The alkoxide of the semi-quinone intermediate initiates a second single electron transfer (forming the first quinone product) through two heme groups to the quinone substrate, which initiates double bond rearrangement generating a semi-quinone intermediate|
|Step 3||Water deprotonates His161, which initiates a single electron transfer from the Rieske iron-sulfur complex to the heme group of cytochrome-c1. Concurrently, water deprotonates Glu272.|
|Step 4||Glu272 deprotonates the second quinol substrate. His161 (bound to a Rieske iron-sulfur cluster) deprotonates the second alcohol group. This initiates a single electron transfer to the Rieske iron-sulfur cluster forming the semi-quinone intermediate.|
|Step 5||The alkoxide of the second semi-quinone intermediate initiates a second single electron transfer (forming the second quinone product) through two heme groups to the semi-quinone substrate, which initiates double bond rearrangement generating the quinol product, that deprotonates Lys228 through a water molecule.|
|Step 6||Water deprotonates His161, which initiates a single electron transfer from the Rieske iron-sulfur complex to the heme group of cytochrome-c1. Concurrently, water deprotonates Glu272.|
|Step 7||Lys228 deprotonates water.|
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Catalytic Residues Involved
||Location of Function
Metal Cofactors for M0208
- A. Y. Mulkidjanian (2005), Biochim. Biophys. Acta, 1709, 5-34. Ubiquinol oxidation in the cytochrome bc1 complex: reaction mechanism and prevention of short-circuiting.
- X. Gao et al. (2003), Biochemistry, 42, 9067-9080. Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site.
- C. Lange et al. (2001), The EMBO Journal, 20, 6591-6600. Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure.
- T. Wenz et al. (2007), J. Biol. Chem., 282, 3977-3988. Mutational analysis of cytochrome b at the ubiquinol oxidation site of yeast complex III.
Homologue information for M0208 (1ezv)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Entries with at least one Catalytic CATH code in common (different mechanisms):
|M0130 ||naphthalene 1,2-dioxygenase |
|M0144 ||arsenite oxidase |
View a comparison of the other reactions in MACiE with the CATH domain 220.127.116.11
Links to this entry in other databases