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Information on EC 7.1.1.9 - cytochrome-c oxidase and Organism(s) Homo sapiens and UniProt Accession P00395

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IUBMB Comments
An oligomeric membrane heme-Cu:O2 reductase-type enzyme that terminates the respiratory chains of aerobic and facultative aerobic organisms. The reduction of O2 to water is accompanied by the extrusion of four protons. The cytochrome-aa3 enzymes of mitochondria and many bacterial species are the most abundant group, but other variations, such as the bacterial cytochrome-cbb3 enzymes, also exist. All of the variants have a conserved catalytic core subunit (subunit I) that contains a low-spin heme (of a- or b-type), a binuclear metal centre composed of a high-spin heme iron (of a-, o-, or b-type heme, referred to as a3, o3 or b3 heme), and a Cu atom (CuB). Besides subunit I, the enzyme usually has at least two other core subunits: subunit II is the primary electron acceptor; subunit III usually does not contain any cofactors, but in the case of cbb3-type enzymes it is a diheme c-type cytochrome. While most bacterial enzymes consist of only 3--4 subunits, the mitochondrial enzyme is much more complex and contains 14 subunits.
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Homo sapiens
UNIPROT: P00395
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
cytochrome c oxidase, cytochrome oxidase, complex iv, cytochrome c oxidase subunit i, cytochrome c oxidase subunit 1, cytochrome aa3, cytochrome-c oxidase, coxii, cytochrome a3, cox ii, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
complex IV (mitochondrial electron transport)
-
-
-
-
COX Vb
-
-
COXVIAH
-
-
-
-
cytochrome a3
-
-
-
-
cytochrome aa3
-
-
-
-
cytochrome ba3
-
-
-
-
cytochrome bb3
-
-
-
-
cytochrome c oxidase
cytochrome C oxidase IV
-
-
Cytochrome caa3
-
-
-
-
cytochrome cbb3
-
-
-
-
cytochrome oxidase
-
-
ferrocytochrome c oxidase
-
-
-
-
indophenol oxidase
-
-
-
-
indophenolase
-
-
-
-
oxidase, cytochrome
-
-
-
-
Warburg's respiratory enzyme
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
reduction
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
ferrocytochrome-c:oxygen oxidoreductase
An oligomeric membrane heme-Cu:O2 reductase-type enzyme that terminates the respiratory chains of aerobic and facultative aerobic organisms. The reduction of O2 to water is accompanied by the extrusion of four protons. The cytochrome-aa3 enzymes of mitochondria and many bacterial species are the most abundant group, but other variations, such as the bacterial cytochrome-cbb3 enzymes, also exist. All of the variants have a conserved catalytic core subunit (subunit I) that contains a low-spin heme (of a- or b-type), a binuclear metal centre composed of a high-spin heme iron (of a-, o-, or b-type heme, referred to as a3, o3 or b3 heme), and a Cu atom (CuB). Besides subunit I, the enzyme usually has at least two other core subunits: subunit II is the primary electron acceptor; subunit III usually does not contain any cofactors, but in the case of cbb3-type enzymes it is a diheme c-type cytochrome. While most bacterial enzymes consist of only 3--4 subunits, the mitochondrial enzyme is much more complex and contains 14 subunits.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-16-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
flavin semiquinone electron donors lumiflavin, riboflavin or FMN can be used, kinetic analysis
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
o-dianisidine + H2O2
?
show the reaction diagram
-
-
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced horse cytochrome c + O2 + H+
oxidized horse cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
accessibility and electrostatic charge of enzyme do not differ in a significant way among human, Arabidopsis thaliana and horse
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
heme a
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
copper
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
amyloid beta
-
native, up to 65% inhibition. Amyloid beta mutation Y10A does not affect maximal inhibition, but the altered peptide needs a longer period for ageing. Substitution M35V or oxidizing the sulfur of M35 to a sulfoxide completely abrogates the peptide’s inhibitory potential. Inhibition depends completely on presence of divalent Cu2+ and may involve the formation of a redox active amyloid-beta-methionine radical
-
amyloid beta1-42
-
synthetic peptide, dimeric amyloid beta specifically inhibits the cytochrome-c oxidase dependent on presence of Cu2+ and specific ageing of the amyloid beta1-42 solution
-
Cu2+
-
inhibition of enzyme by amyloid beta depends completely on presence of divalent Cu2+, but not Cu+
KCN
-
1 mM results in a sustained 50% loss of activity following 24, 48 and 72 h of culture
nitric oxide
siRNA
-
small interfering RNA against Vb selectively lowers COX Vb expression in HeLa-80 cells, increases mitochondrial reactive oxygen species generation, decreases COX activity 60-80%, and diminishes viability under 80% (but not 20%) O2
-
Sodium azide
-
the addition of 0.5 mM sodium azide at 0.1 mM O2during the initial purging process results in a maximal reduction in cytochrome c oxidase redox state
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Surf1
-
biogenesis of mitochondrial cytochrome c oxidase relies on a large number of assembly factors, among them the transmembrane protein Surf1
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00005 - 0.002
ferrocytochrome c
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
30 - 80
ferrocytochrome c
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
CN-
Homo sapiens
-
-
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
9.6
-
calculated
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
lymphoblastoid cells prepared from leucocytes
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
enzyme deficiency manifests as the Leigh syndrome in humans
metabolism
-
the cytochrome c oxidase plays an important role in regulating endogenous nitric oxide concentrations
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
COX1_HUMAN
513
12
57041
Swiss-Prot
Secretory Pathway (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12233
-
x * 12233, MALDI-TOF, x * 12236, calculated
12236
-
x * 12233, MALDI-TOF, x * 12236, calculated
13700
-
I, II, III, IV, V, VI, VII, 1 * 43600 + 1 * 20100 + 1* 18000 + 1 * 13700 + 1 * 8800 + 1 * 5600 + 1 * 3700, SDS-PAGE
20100
-
I, II, III, IV, V, VI, VII, 1 * 43600 + 1 * 20100 + 1* 18000 + 1 * 13700 + 1 * 8800 + 1 * 5600 + 1 * 3700, SDS-PAGE
43600
-
I, II, III, IV, V, VI, VII, 1 * 43600 + 1 * 20100 + 1* 18000 + 1 * 13700 + 1 * 8800 + 1 * 5600 + 1 * 3700, SDS-PAGE
5600
-
I, II, III, IV, V, VI, VII, 1 * 43600 + 1 * 20100 + 1* 18000 + 1 * 13700 + 1 * 8800 + 1 * 5600 + 1 * 3700, SDS-PAGE
8800
-
I, II, III, IV, V, VI, VII, 1 * 43600 + 1 * 20100 + 1* 18000 + 1 * 13700 + 1 * 8800 + 1 * 5600 + 1 * 3700, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 12233, MALDI-TOF, x * 12236, calculated
oligomer
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A122T
recurrent missense mutation in mitochondrially encoded cytochrome oxidase I found in a variety of human cancer cells
G6930A
-
nonsense mutation in the mitochondrially encoded complex IV subunit 1 gene, which causes a disruption in the assembly and defective activity of complex VI
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA of subunits IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIc, VIII
-
COX subunit Vb open reading frame ligated into the pcDNA3.1/V5-His TOPO-TA expression vector and transfected into TOP10 Escherichia coli. Overexpression in HeLa-20 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Leigh syndrome most frequent trigger is deficiency of cytochrome c oxidase caused by mutations in the SURF1 gene
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
A122T, i.e. m.6267G>A is a recurrent missense mutation in mitochondrially encoded cytochrome oxidase I specifically associated with cancer
medicine
additional information
-
an assembled complex IV helps to maintain complex I (NADH-ubiquinone oxidoreductase) in mammalian cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Azzi, A.
Cytochrome c oxidase. Towards a clarification of its structure, interactions and mechanism
Biochim. Biophys. Acta
594
231-252
1980
Bos taurus, Saccharomyces cerevisiae, eukaryota, Homo sapiens, Neurospora crassa, Rattus norvegicus
Manually annotated by BRENDA team
Lomax, M.I.; Grossman, L.I.
Tissue-specific genes for respiratory proteins [published erratum appears in Trends Biochem Sci 1990 Jun;15(6):217]
Trends Biochem. Sci.
14
501-503
1989
Bos taurus, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Sinjorgo, K.M.C.; Hakvoort, T.B.M.; Durak, I.; Draijer, J.W.; Post, J.K.P.; Muijsers, A.O.
Human cytochrome c oxidase isoenzymes from heart and skeletal muscle: purification and properties
Biochim. Biophys. Acta
850
144-150
1987
Homo sapiens
-
Manually annotated by BRENDA team
Kadenbach, B.; Stroh, A.; Ungibauer, M.; Kuhn-Nentwig, L.; Buge, U.; Jarausch, J.
Isozymes of cytochrome-c oxidase: characterization and isolation from different tissues
Methods Enzymol.
126
32-45
1986
Martes foina, Bos taurus, Gallus gallus, Cervidae, Homo sapiens, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Rodriguez-Roldan, V.; Garcia-Heredia, J.M.; Navarro, J.A.; Hervas, M.; De la Cerda, B.; Molina-Heredia, F.P.; De la Rosa, M.A.
A comparative kinetic analysis of the reactivity of plant, horse, and human respiratory cytochrome c towards cytochrome c oxidase
Biochem. Biophys. Res. Commun.
346
1108-1113
2006
Arabidopsis thaliana, Equus caballus, Homo sapiens
Manually annotated by BRENDA team
Stiburek, L.; Vesela, K.; Hansikova, H.; Pecina, P.; Tesarova, M.; Cerna, L.; Houstek, J.; Zeman, J.
Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1
Biochem. J.
392
625-632
2005
Homo sapiens
Manually annotated by BRENDA team
Gallardo, M.E.; Moreno-Loshuertos, R.; Lopez, C.; Casqueiro, M.; Silva, J.; Bonilla, F.; Rodriguez de Cordoba, S.; Enriquez, J.A.
m.6267G>A: a recurrent mutation in the human mitochondrial DNA that reduces cytochrome c oxidase activity and is associated with tumors
Hum. Mutat.
27
575-582
2006
Homo sapiens (P00395), Homo sapiens
Manually annotated by BRENDA team
Williams, J.C.; Sue, C.; Banting, G.S.; Yang, H.; Glerum, D.M.; Hendrickson, W.A.; Schon, E.A.
Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein
J. Biol. Chem.
280
15202-15211
2005
Homo sapiens
Manually annotated by BRENDA team
Campian, J.L.; Gao, X.; Qian, M.; Eaton, J.W.
Cytochrome C oxidase activity and oxygen tolerance
J. Biol. Chem.
282
12430-12438
2007
Homo sapiens
Manually annotated by BRENDA team
Palacios-Callender, M.; Hollis, V.; Frakich, N.; Mateo, J.; Moncada, S.
Cytochrome c oxidase maintains mitochondrial respiration during partial inhibition by nitric oxide
J. Cell Sci.
120
160-165
2007
Homo sapiens
Manually annotated by BRENDA team
Wang, X.Z.; Li, D.; Tao, Q.M.; Lin, N.; Chen, Z.X.
A novel hepatitis B virus X-interactive protein: cytochrome C oxidase III
J. Gastroenterol. Hepatol.
21
711-715
2006
Homo sapiens
Manually annotated by BRENDA team
Crouch, P.J.; Barnham, K.J.; Duce, J.A.; Blake, R.E.; Masters, C.L.; Trounce, I.A.
Copper-dependent inhibition of cytochrome c oxidase by Abeta(1-42) requires reduced methionine at residue 35 of the Abeta peptide
J. Neurochem.
99
226-236
2006
Homo sapiens
Manually annotated by BRENDA team
Crouch, P.J.; Blake, R.; Duce, J.A.; Ciccotosto, G.D.; Li, Q.X.; Barnham, K.J.; Curtain, C.C.; Cherny, R.A.; Cappai, R.; Dyrks, T.; Masters, C.L.; Trounce, I.A.
Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42
J. Neurosci.
25
672-679
2005
Homo sapiens
Manually annotated by BRENDA team
Hargreaves, I.P.; Duncan, A.J.; Wu, L.; Agrawal, A.; Land, J.M.; Heales, S.J.
Inhibition of mitochondrial complex IV leads to secondary loss complex II-III activity: implications for the pathogenesis and treatment of mitochondrial encephalomyopathies
Mitochondrion
7
284-287
2007
Homo sapiens
Manually annotated by BRENDA team
Durham, S.E.; Samuels, D.C.; Cree, L.M.; Chinnery, P.F.
Normal levels of wild-type mitochondrial DNA maintain cytochrome c oxidase activity for two pathogenic mitochondrial DNA mutations but not for m.3243A-->G
Am. J. Hum. Genet.
81
189-195
2007
Homo sapiens
Manually annotated by BRENDA team
Napoli, E.; Morin, D.; Bernhardt, R.; Buckpitt, A.; Cortopassi, G.
Hemin rescues adrenodoxin, heme a and cytochrome oxidase activity in frataxin-deficient oligodendroglioma cells
Biochim. Biophys. Acta
1772
773-780
2007
Homo sapiens
Manually annotated by BRENDA team
Murray, J.; Schilling, B.; Row, R.H.; Yoo, C.B.; Gibson, B.W.; Marusich, M.F.; Capaldi, R.A.
Small-scale immunopurification of cytochrome c oxidase for a high-throughput multiplexing analysis of enzyme activity and amount
Biotechnol. Appl. Biochem.
48
167-178
2007
Bos taurus, Bos taurus (P00396), Bos taurus (P00415), Bos taurus (P00423), Bos taurus (P00426), Bos taurus (P00428), Bos taurus (P00429), Bos taurus (P00430), Bos taurus (P04038), Bos taurus (P07470), Bos taurus (P07471), Bos taurus (P10175), Bos taurus (P13183), Bos taurus (P13184), Homo sapiens
Manually annotated by BRENDA team
Fontanesi, F.; Jin, C.; Tzagoloff, A.; Barrientos, A.
Transcriptional activators HAP/NF-Y rescue a cytochrome c oxidase defect in yeast and human cells
Hum. Mol. Genet.
17
775-788
2008
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Li, Y.; DAurelio, M.; Deng, J.H.; Park, J.S.; Manfredi, G.; Hu, P.; Lu, J.; Bai, Y.
An assembled complex IV maintains the stability and activity of complex I in mammalian mitochondria
J. Biol. Chem.
282
17557-17562
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Bundschuh, F.A.; Hannappel, A.; Anderka, O.; Ludwig, B.
Surf1, associated with Leigh syndrome in humans, is a heme-binding protein in bacterial oxidase biogenesis
J. Biol. Chem.
284
25735-25741
2009
Homo sapiens
Manually annotated by BRENDA team
Unitt, D.; Hollis, V.; Palacios-Callender, M.; Frakich, N.; Moncada, S.
Inactivation of nitric oxide by cytochrome c oxidase under steady-state oxygen conditions
Biochim. Biophys. Acta
1797
371-377
2010
Homo sapiens
Manually annotated by BRENDA team
Kovarova, N.; Pecina, P.; Nuskova, H.; Vrbacky, M.; Zeviani, M.; Mracek, T.; Viscomi, C.; Houstek, J.
Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects
Biochim. Biophys. Acta
1862
705-715
2016
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Zsengeller, Z.K.; Rosen, S.
The use of cytochrome c oxidase enzyme activity and immunohistochemistry in defining mitochondrial injury in kidney disease
J. Histochem. Cytochem.
64
546-555
2016
Homo sapiens
Manually annotated by BRENDA team