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Overview for MACiE Entry M0208

Version history

General Information

EC Number: 1.10.2.2 (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
  • 2.60.40.10 - Immunoglobulins
  • 3.30.830.10 - Cytochrome Bc1 Complex; Chain A, domain 1
  • 1.20.5.210 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
  • 1.10.1090.10 - Cytochrome Bc1 Complex; Chain F
  • 1.20.5.100 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
  • 1.10.287.20 - Helix Hairpins
  • 1.20.5.270 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces
  • 1.20.5.260 - Single alpha-helices involved in coiled-coils or other helix-helix interfaces

Display structure information

Overall Reaction:

Image of Ubiquinone

Image of Ubiquinol

Image of Ferricytochrome c

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Image of Ubiquinone

Image of Proton

Image of Ubiquinol

Image of Ferrocytochrome c

Ubiquinone
C00399
CHEBI:16389
2 Ubiquinol
C00390
CHEBI:17976
2 Ferricytochrome c
C00125
CHEBI:15991
2 Ubiquinone
C00399
CHEBI:16389
2 Proton
C00080
CHEBI:24636
Ubiquinol
C00390
CHEBI:17976
2 Ferrocytochrome c
C00126
CHEBI:16928

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 [2] 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.


View similar reactions


Stepwise Description of the Reaction

Step 1Glu272 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 2The 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 3Water 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 4Glu272 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 5The 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 6Water 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 7Lys228 deprotonates water.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
His 161 E Side Chain
Glu 272 C Side Chain
His 202 C Side Chain
Lys 228 C Side Chain
Asp 229 C Side Chain
Ser 206 C Side Chain

Metal Cofactors for M0208

Type Het group Number Chain
iron HEM 401 C Overview
iron HEM 402 C Overview
iron HEM 3 D Overview
iron FES 4 E Overview

References

  1. A. Y. Mulkidjanian (2005), Biochim. Biophys. Acta, 1709, 5-34. Ubiquinol oxidation in the cytochrome bc1 complex: reaction mechanism and prevention of short-circuiting.
    Medline: 16005845
  2. 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.
    Medline: 12885240
  3. C. Lange et al. (2001), The EMBO Journal, 20, 6591-6600. Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure.
    Medline: 11726495
  4. 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.
    Medline: 17145759

Homologue information for M0208 (1ezv)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0130 naphthalene 1,2-dioxygenase
1.14.12.12
1ndo 2.102.10.10
0.19350.5625Compare
M0144 arsenite oxidase
1.20.98.1
1g8k 2.102.10.10
0.06870.4199Compare

View a comparison of the other reactions in MACiE with the CATH domain 2.102.10.10


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
catalytic activity (molecular function)
metalloendopeptidase activity (molecular function)
iron ion binding (molecular function)
mitochondrial envelope (cellular component)
mitochondrial electron transport, ubiquinol to cytochrome c (biological process)
proteolysis (biological process)
ubiquinol-cytochrome-c reductase activity (molecular function)
zinc ion binding (molecular function)
electron carrier activity (molecular function)
membrane (cellular component)
oxidoreductase activity (molecular function)
oxidoreductase activity, acting on diphenols and related substances as donors (molecular function)
heme binding (molecular function)
respiratory electron transport chain (biological process)
metal ion binding (molecular function)
2 iron, 2 sulfur cluster binding (molecular function)
oxidation-reduction process (biological process)
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