Information on EC 1.9.3.1 - cytochrome-c oxidase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY
1.9.3.1
-
RECOMMENDED NAME
GeneOntology No.
cytochrome-c oxidase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
reaction mechanism
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
proposed mechanism of proton translocation
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of O2 reduction
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of O2 reduction
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of O2 reduction
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
steady-state kinetics
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
study of primary intermediates in the reaction of O2 with the fully reduced enzyme
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
proposal for complete turnover cycle, i.e. intramolecular electron transfer, O2 reduction and proton pumping
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
reaction mechanism of cytochrome c with O2
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
schematic diagram of cytochrome c oxidase
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of proton pumping
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of proton pumping
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of proton pumping
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of proton pumping
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
mechanism of proton pumping
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
proposed electron transfer pathway within the cytochrome c-cytochrome c oxidase complex
-
4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O
show the reaction diagram
spectra of the A, PM, F and O itnermediate state of enzyme catalysis by use of a special cuvette to measure optical changes of millisecond freeze-hyperquench powder samples at temperatures below -23C. Catalytic cycle of cytochrome c oxidase at low temperature is similar to that at room temperature
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
aerobic respiration I (cytochrome c)
-
-
aerobic respiration II (cytochrome c) (yeast)
-
-
arsenite oxidation I (respiratory)
-
-
Fe(II) oxidation
-
-
Metabolic pathways
-
-
Oxidative phosphorylation
-
-
oxidative phosphorylation
-
-
SYSTEMATIC NAME
IUBMB Comments
ferrocytochrome-c:oxygen oxidoreductase
A cytochrome of the a type containing copper. The reduction of O2 to water is accompanied by the extrusion of four protons from the intramitochondrial compartment. Several bacteria appear to contain analogous oxidases.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A-protein
-
-
-
-
AED
-
-
-
-
complex IV (mitochondrial electron transport)
-
-
-
-
COXVIAH
-
-
-
-
cytochrome a3
-
-
-
-
cytochrome aa3
-
-
-
-
cytochrome c oxidase
-
-
-
-
Cytochrome caa3
-
-
-
-
cytochrome oxidase
-
-
-
-
ferrocytochrome c oxidase
-
-
-
-
Fourth terminal oxidase
-
-
-
-
IHQ
-
-
-
-
indophenol oxidase
-
-
-
-
indophenolase
-
-
-
-
NADH cytochrome c oxidase
-
-
-
-
oxidase, cytochrome
-
-
-
-
Polypeptide VIb
-
-
-
-
SSG
-
-
-
-
STA
-
-
-
-
VIA*
-
-
-
-
VIIaL
-
-
-
-
VIIIA
-
-
-
-
VIIIb
-
-
-
-
VIIIC
-
-
-
-
Warburg's respiratory enzyme
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9001-16-5
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strains MON-1, AP19-3 and ATCC 23270
-
-
Manually annotated by BRENDA team
PCC6301
-
-
Manually annotated by BRENDA team
Anabaena sp. PCC6301
PCC6301
-
-
Manually annotated by BRENDA team
nitrogen-fixing cyanobacterium
-
-
Manually annotated by BRENDA team
ecotype Columbia
-
-
Manually annotated by BRENDA team
recombinant enzyme expressed in Escherichia coli, comparison with human and horse enzyme
-
-
Manually annotated by BRENDA team
strain W23
-
-
Manually annotated by BRENDA team
Bacillus subtilis W23
strain W23
-
-
Manually annotated by BRENDA team
; overview
-
-
Manually annotated by BRENDA team
comparison of two oxidized states of enzyme, the state as isolated in the fast form, and the form obtained immediately after oxidation of fully reduced cytochrome-c oxidase with O2. No observable differences are found between these two states
-
-
Manually annotated by BRENDA team
model based on bovine sequence
-
-
Manually annotated by BRENDA team
blacknose shark
-
-
Manually annotated by BRENDA team
black tip reef shark
-
-
Manually annotated by BRENDA team
dusty shark
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
recombinant enzyme expressed in Escherichia coli, comparison with human and Arabidosis thaliana enzyme
-
-
Manually annotated by BRENDA team
aerobic photoheterotroph
-
-
Manually annotated by BRENDA team
synthetic model of cytochrome C oxidase
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
tiger shark
-
-
Manually annotated by BRENDA team
formerly Bacillus stearothermophilus strain K1041
-
-
Manually annotated by BRENDA team
Geobacillus thermodenitrificans K1041
formerly Bacillus stearothermophilus strain K1041
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
isoform cytochrome oxidase III
-
-
Manually annotated by BRENDA team
patients with mutations in genes SCO2 or SURF1 affecting enzyme assembly
-
-
Manually annotated by BRENDA team
recombinant enzyme expressed in Escherichia coli, comparison with Arabidopsis thaliana and horse enzyme
-
-
Manually annotated by BRENDA team
sweet potato
-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
Metapenaeus sp.
-
-
-
Manually annotated by BRENDA team
lysodeikticus
-
-
Manually annotated by BRENDA team
B6.129S4-Prkce/tm1/Msg/J mice and Prcke/tm1/Msg-2-3
-
-
Manually annotated by BRENDA team
C57B6/S129 mice
SwissProt
Manually annotated by BRENDA team
C57BL/6 mice
-
-
Manually annotated by BRENDA team
Girk2(Wv) (Weaver) mutant mice
-
-
Manually annotated by BRENDA team
male C57Bl6 mice
-
-
Manually annotated by BRENDA team
subunit IV isoform 2; subunit IV isoform 2
SwissProt
Manually annotated by BRENDA team
Mus musculus C57B6/S129
C57B6/S129 mice
SwissProt
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
-
-
Manually annotated by BRENDA team
individuals with SM and RM mitochondrial genomes are differentiated with the amplification of a 750 bp region of the cox1 gene, accession numbers EU018148 to EU018204; male, standard male, SM, and recently masculinized, RM, types
UniProt
Manually annotated by BRENDA team
cultivar BY-2
-
-
Manually annotated by BRENDA team
no activity in Escherichia coli
-
-
-
Manually annotated by BRENDA team
PCC8009
-
-
Manually annotated by BRENDA team
Nostoc sp. PCC8009
PCC8009
-
-
Manually annotated by BRENDA team
animals suffering from enzootic ataxia i.e. swayback-disease
-
-
Manually annotated by BRENDA team
subunit 1-beta and subunit 2
P98002 and P08306
UniProt
Manually annotated by BRENDA team
Paracoccus denitrificans AO1
subunit 1-beta and subunit 2
P98002 and P08306
UniProt
Manually annotated by BRENDA team
strain IFO 3445
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa IFO
strain IFO 3445
-
-
Manually annotated by BRENDA team
Accession number of subunit 2 of Aa3 oxidase; strain KT2240
UniProt
Manually annotated by BRENDA team
Pseudomonas putida KT2240
Accession number of subunit 2 of Aa3 oxidase; strain KT2240
UniProt
Manually annotated by BRENDA team
Pseudomonas sp. AM1
AM1
-
-
Manually annotated by BRENDA team
adult male albino rats of Charles-Foster strain
-
-
Manually annotated by BRENDA team
adult male Wistar rats
-
-
Manually annotated by BRENDA team
female Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Wistar rats
-
-
Manually annotated by BRENDA team
young adult female Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Rattus norvegicus Charles-Foster
adult male albino rats of Charles-Foster strain
-
-
Manually annotated by BRENDA team
atlantic sharpnose shark
-
-
Manually annotated by BRENDA team
cbb3-type cytochrome-c oxidase, CcoN subunit
SwissProt
Manually annotated by BRENDA team
purple non-sulfur bacterium
-
-
Manually annotated by BRENDA team
thermohalophilic bacterium
-
-
Manually annotated by BRENDA team
strain BY4742
-
-
Manually annotated by BRENDA team
strains W303-1A , DELTAshy1 and W125
-
-
Manually annotated by BRENDA team
Saccharomyces cerevisiae BY4742
strain BY4742
-
-
Manually annotated by BRENDA team
fragment
UniProt
Manually annotated by BRENDA team
scallop hammerhead shark
-
-
Manually annotated by BRENDA team
spiny dogfish, overview
-
-
Manually annotated by BRENDA team
all 44 partially or totally sequenced cyanobacterial genomes are analyzed for the occurence of cytM and its putative electron acceptor cytochrome c oxidase
-
-
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
cytochrome c oxidase polypeptide I and III
UniProt
Manually annotated by BRENDA team
subunit 1
UniProt
Manually annotated by BRENDA team
var. Titan Red, wheat
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
a site-specific target disturbance of the electron transport chain at complex IV is a possible source for CH4 formation in plant cells
metabolism
-
cytochrome c oxidase is the terminal enzyme in the respiratory electron transport chain of mitochondria. It catalyzes the reduction of oxygen to water to generate the electrochemical proton gradient across the mitochondrial membrane that powers the production of ATP. The enzyme takes up four electrons from the positively charged P side (outside) of the membrane and four protons from the negatively charged N side (inside) for the reduction of dioxygen to two water molecules
metabolism
-
the cytochrome c oxidase plays an important role in regulating endogenous nitric oxide concentrations
physiological function
-
the enzyme is a specific intra-mitochondrial site of age-related deterioration, which has a broad impact on mitochondrial physiology. The decline in enzyme activity during aging is associated with selective losses in the levels of both nuclear and mitochondrial DNA-encoded enzyme subunits
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,3,5,6-tetramethyl-p-phenylendiamine + O2 + H+
? + H2O
show the reaction diagram
-
-
-
-
-
2,3,5,6-tetramethyl-p-phenylenediamine + O2
? + H2O
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Charles-Foster
-
-
-
-
?
3,3'-diaminobenzidene-tetrahydrochloride + O2 + H+
? + H2O
show the reaction diagram
-
-
-
-
?
3,3'-diaminobenzidene-tetrahydrochloride + O2 + H+
? + H2O
show the reaction diagram
Mus musculus, Mus musculus C57B6/S129
P17665
-
-
-
?
amidopyrine + H2O2
?
show the reaction diagram
-
-
-
-
?
ascorbate + O2
?
show the reaction diagram
-
-
-
-
?
ascorbate + O2
? + H2O
show the reaction diagram
-
reaction of enzyme in detergent solution and reconstituted in phospholipid vesicles
-
-
?
benzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
diaminobenzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
Q5SJ79, Q5SJ80, Q72H23
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
P98005
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
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
ferricytochrome c + H2O
show the reaction diagram
-
Nitrobacter agilis ferrocytochrome c552
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
proton translocation across eukaryotic mitochondrial and prokyryotic cytoplasmic membrane, overview proposed mechanims
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
proton translocation across eukaryotic mitochondrial and prokyryotic cytoplasmic membrane, overview proposed mechanims
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Saccharomyces cerevisiae cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Saccharomyces cerevisiae cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Saccharomyces cerevisiae cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Saccharomyces cerevisiae cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Saccharomyces cerevisiae cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Magnetospirillum magnetotacticum cytochrome c550
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: 2,6-dichlorophenolindophenol
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
reaction intermediates
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
additional electron donor: rusticyanin, i.e. a copper protein from Thiobacillus ferrooxidans
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Saccharomyces oviformis cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
horse ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/diaminodurene
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: phenazine methosulfate
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: phenazine methosulfate
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: phenazine methosulfate
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: phenazine methosulfate
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
cow cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
cow cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
cytochrome c550 and cytochrome c549
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Crithidia fasciculata cytochrome c
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
ferrocytochrome c550
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
ferrocytochrome c552
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
no proton translocation
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
tuna cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
tuna cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/hexaamine ruthenium
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Candida krusei ferrocytochrome c
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Candida krusei ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Candida krusei ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Candida krusei ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Candida krusei ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Candida krusei ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
Nitrosomonas europaea cytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
overview additional activities i.e. catalase activity, peroxidase activity, superoxide dismutase activity, carbomonoxygenase activity
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
-
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
coordinated down regulation of mitochondrial genome-coded CytOX I and CytOX II and nuclear genome-coded CytOX IV and Vb mRNAs during hypoxia
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
cytochrome c6 is at least one of the endogenous electron donors. In the thylakoid lumen cytochrome c6 can deliver electrons to cytochrome c oxidase
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
terminal enzyme of the electron transport chain. The glucagon receptor/G-protein/c-AMP pathway regulates enzyme activity
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
Pseudomonas sp. AM1
-
horse ferrocytochrome c, Candida krusei ferrocytochrome c
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
Bacillus subtilis W23
-
artificial electron donor: ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
P00396, P00415, P00423, P00426, P00428, P00429, P00430, P04038, P07470, P07471, P10175, P13183, P13184
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
synthetic construct
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
Paracoccus denitrificans, Paracoccus denitrificans AO1
P98002 and P08306
-
-
-
?
ferrocytochrome c(H) + O2
ferricytochrome c(H) + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c-550 + O2
ferricytochrome c-550 + H2O
show the reaction diagram
-
-
-
-
?
N,N,N',N'-tetramethyl-p-phenylenediamine + O2
?
show the reaction diagram
-
-
-
-
?
o-dianisidine + H2O2
?
show the reaction diagram
-
-
-
-
?
o-dianisidine + H2O2
?
show the reaction diagram
-
-
-
-
?
oxidized horse heart cytochrome c + H2O
reduced horse heart cytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
p-phenylenediamine + H2O2
?
show the reaction diagram
-
-
-
-
?
peroxynitrite
NO + O22-
show the reaction diagram
-
enzyme must be fully reduced, proposed reaction
-
?
reduced Aspergillus oryzae cytochrome c + O2
oxidized Aspergillus oryzae cytochrome c + H2O
show the reaction diagram
-
relative activity 2.2%
-
-
?
reduced Bacillus subtilis cytochrome c + O2
oxidized Bacillus subtilis cytochrome c + H2O
show the reaction diagram
-
relative activity 27%
-
-
?
reduced Bos taurus cytochrome c + O2
oxidized Bos taurus cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced Bos taurus cytochrome c + O2
oxidized Bos taurus cytochrome c + H2O
show the reaction diagram
-
relative activity 0.53%
-
-
?
reduced Bos taurus cytochrome c + O2
oxidized Bos taurus cytochrome c + H2O
show the reaction diagram
Mus musculus C57BL/6
-
-
-
-
?
reduced Bos taurus cytochrome c + O2 + H+
oxidized Bos taurus cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced Bufo vulgaris cytochrome c + O2
oxidized Bufo vulgaris cytochrome c + H2O
show the reaction diagram
-
relative activity 0.73%
-
-
?
reduced Candida krusei cytochrome c + O2
oxidized Candida krusei cytochrome c + H2O
show the reaction diagram
-
relative activity 5.0%
-
-
?
reduced Columba livia cytochrome c + O2
oxidized Columba livia cytochrome c + H2O
show the reaction diagram
-
relative activity 0.44%
-
-
?
reduced cytochrome aa3 + O2 + H+
oxidized cytochrome aa3 + H2O
show the reaction diagram
-
formation of a tryptophan-radical intermediate (tryptophan neutral radical of the strictly conserved Trp-272). The formation of the Trp-272 constitutes the major rate-determining step of the catalytic cycle
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
electron exchange of cytochrome c with the electrode with CcO (with a his-tag at the C-terminus of subunit I) immobilized in a protein-tethered bilayer lipid membrane is shown to be mediated by the enzyme if oxygen is present in the bulk solution. The increasing current density in the anodic and cathodic direction in the presence of oxygen may be due to intermediate redox states of the CcO. Hopping mechanism of electron transfer through the enzyme between cytochrome c and the electrode
-
-
?
reduced cytochrome c + O2 + H+
oxidized cytochrome c + H2O
show the reaction diagram
-
oxidation of cytochrome c by cytochrome oxidase stimulates caspase activation
-
-
?
reduced cytochrome c551 + O2 + H+
oxidized cytochrome c551 + H2O
show the reaction diagram
Geobacillus thermodenitrificans, Geobacillus thermodenitrificans K1041
-
-
-
-
?
reduced Homo sapiens cytochrome c + O2
oxidized Homo sapiens cytochrome c + H2O
show the reaction diagram
-
relative activity 0.44%
-
-
?
reduced horse cytochrome c + O2
oxidized horse cytochrome c + H2O
show the reaction diagram
Pseudomonas aeruginosa, Pseudomonas aeruginosa IFO
-
-
-
-
?
reduced horse cytochrome c + O2 + H+
oxidized horse cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced horse cytochrome c + O2 + H+
oxidized horse cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced horse heart cytochrome c + O2 + H+
oxidized horse heart cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced horse heart cytochrome c + O2 + H+
oxidized horse heart cytochrome c + H2O
show the reaction diagram
-
-
-
-
?
reduced Kloeckera sp. cytochrome c + O2
oxidized Kloeckera sp. cytochrome c + H2O
show the reaction diagram
-
relative activity 5.4%
-
-
?
reduced Loligo pealeii cytochrome c + O2
oxidized Loligo pealeii cytochrome c + H2O
show the reaction diagram
-
relative activity 1.2%
-
-
?
reduced Musca domestica cytochrome c + O2
oxidized Musca domestica cytochrome c + H2O
show the reaction diagram
-
relative activity 2.6%
-
-
?
reduced N,N,N',N'-tetramethyl-p-phenylene diamine + O2
oxidized N,N,N',N'-tetramethyl-p-phenylene diamine + H2O
show the reaction diagram
Pseudomonas aeruginosa, Pseudomonas aeruginosa IFO
-
-
-
-
?
reduced oyster cytochrome c + O2
oxidized oyster cytochrome c + H2O
show the reaction diagram
-
relative activity 0.54%
-
-
?
reduced Physarum polycephalum cytochrome c + O2
oxidized Physarum polycephalum cytochrome c + H2O
show the reaction diagram
-
relative activity 0.9%
-
-
?
reduced Porphyra tenera cytochrome c + O2
oxidized Porphyra tenera cytochrome c + H2O
show the reaction diagram
-
relative activity 15%
-
-
?
reduced prawn cytochrome c + O2
oxidized prawn cytochrome c + H2O
show the reaction diagram
-
relative activity 0.95%
-
-
?
reduced Pseudomonas aeruginosa cytochrome c + O2
oxidized Pseudomonas aeruginosa cytochrome c + H2O
show the reaction diagram
-
relativ activity 100%
-
-
?
reduced Pseudomonas saccharophila cytochrome c + O2
oxidized Pseudomonas saccharophila cytochrome c + H2O
show the reaction diagram
-
relative activity 82%
-
-
?
reduced Rhodospirillum rubrum cytochrome c + O2
oxidized Rhodospirillum rubrum cytochrome c + H2O
show the reaction diagram
-
relative activity 1.7%
-
-
?
reduced Saccharomyces cerevisiae cytochrome c + O2
oxidized Saccharomyces cerevisiae cytochrome c + H2O
show the reaction diagram
-
relative activity 4.9%
-
-
?
reduced salmon cytochrome c + O2
oxidized salmon cytochrome c + H2O
show the reaction diagram
-
relative activity 7.1%
-
-
?
reduced Scombridae gen. sp. cytochrome c + O2
oxidized Scombridae gen. sp. cytochrome c + H2O
show the reaction diagram
-
relative activity 8.7%
-
-
?
reduced shark cytochrome c + O2
oxidized shark cytochrome c + H2O
show the reaction diagram
-
relative activity 1.5%
-
-
?
reduced Styela plicata cytochrome c + O2
oxidized Styela plicata cytochrome c + H2O
show the reaction diagram
-
relative activity 2.2%
-
-
?
reduced Triticum aestivum cytochrome c + O2
oxidized Triticum aestivum cytochrome c + H2O
show the reaction diagram
-
relative activity 1.5%
-
-
?
reduced yeast cytochrome c + O2
oxidized yeast cytochrome c + H2O
show the reaction diagram
Pseudomonas aeruginosa, Pseudomonas aeruginosa IFO
-
-
-
-
?
tetramethyl-phenylenediamine + O2 + H+
? + H2O
show the reaction diagram
-
-
-
-
?
tetramethylbenzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
melatonin + H2O2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the predominant entry point for protons going into the K-channel of cytochrome oxidase is the surface-exposed glutamic acid E101 in subunit II
-
-
-
additional information
?
-
-
thyroid hormone T3 regulates the expression of COX subunits by both transcriptional and posttranslational mechanism
-
-
-
additional information
?
-
-
antioxidant enzyme activities may not be enhanced as part of adaptation in arctic fishes, at least not in the liver
-
-
-
additional information
?
-
-
accessibility and electrostatic charge of enzyme do not differ in a significant way among human, Arabidopsis thaliana and horse
-
-
-
additional information
?
-
Q88RM6
For all mutant strains, the NADH oxidation activity of membranes obtained from aerobic exponentially growing cultures is some higher than that of the wild-type strain (in the range of 1035% higher), inactivation of the Cbb3-1 terminal oxidase in a strain containing a wild-type ANR gene lead to a 46% decrease in cytochrome b and to a 57% decrease in cytochrome c
-
-
-
additional information
?
-
-
numerous organic aromatic compounds, which are not oxidized by cytochrome oxidase via the oxidase mechanism (i.e. using molecular oxygen as the terminal acceptor), can undergo a low rate oxidation by cytochrome oxidase via the peroxidase mechanism. Paracetamol and isonicotinic acid hydrazide are completely resistant to peroxidation by cytochrome oxidase
-
-
-
additional information
?
-
synthetic construct
-
oxygenation of the tetradentate model both in MeCN and in other solvents produces a low-temperature-stable dioxygen-bridged peroxide with an O-O stretching vibration at 799 cm-1. Oxygenation of the tridentate model in EtCN solution generates a heme superoxide species with the copper moiety oxidized to copper(II). Coexistence of a heme superoxide and a bridged peroxide species in equivalent amounts when the oxygenation reaction is carried out in CH2Cl2/7% EtCN
-
-
-
additional information
?
-
-
the intermolecular electron transfer kinetics between CytcM and the soluble CuA domain, i.e. the donor binding and electron entry site, of subunit II of cytochrome c oxidase is investigated
-
-
-
additional information
?
-
-
cytochrome c oxidase is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, the enzyme translocates protons across the membrane against this potential
-
-
-
additional information
?
-
Pseudomonas putida KT2240
Q88RM6
For all mutant strains, the NADH oxidation activity of membranes obtained from aerobic exponentially growing cultures is some higher than that of the wild-type strain (in the range of 1035% higher), inactivation of the Cbb3-1 terminal oxidase in a strain containing a wild-type ANR gene lead to a 46% decrease in cytochrome b and to a 57% decrease in cytochrome c
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
-
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
Q5SJ79, Q5SJ80, Q72H23
-
-
-
?
ferricytochrome c + H2O
ferrocytochrome c + O2 + H+
show the reaction diagram
P98005
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
coordinated down regulation of mitochondrial genome-coded CytOX I and CytOX II and nuclear genome-coded CytOX IV and Vb mRNAs during hypoxia
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
cytochrome c6 is at least one of the endogenous electron donors. In the thylakoid lumen cytochrome c6 can deliver electrons to cytochrome c oxidase
-
-
?
ferrocytochrome c + O2
ferricytochrome c + H2O
show the reaction diagram
-
terminal enzyme of the electron transport chain. The glucagon receptor/G-protein/c-AMP pathway regulates enzyme activity
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
-
-
-
-
?
ferrocytochrome c + O2 + H+
ferricytochrome c + H2O
show the reaction diagram
Paracoccus denitrificans, Paracoccus denitrificans AO1
P98002 and P08306
-
-
-
?
ferrocytochrome c(H) + O2
ferricytochrome c(H) + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the predominant entry point for protons going into the K-channel of cytochrome oxidase is the surface-exposed glutamic acid E101 in subunit II
-
-
-
additional information
?
-
-
thyroid hormone T3 regulates the expression of COX subunits by both transcriptional and posttranslational mechanism
-
-
-
additional information
?
-
-
antioxidant enzyme activities may not be enhanced as part of adaptation in arctic fishes, at least not in the liver
-
-
-
additional information
?
-
Q88RM6
For all mutant strains, the NADH oxidation activity of membranes obtained from aerobic exponentially growing cultures is some higher than that of the wild-type strain (in the range of 1035% higher), inactivation of the Cbb3-1 terminal oxidase in a strain containing a wild-type ANR gene lead to a 46% decrease in cytochrome b and to a 57% decrease in cytochrome c
-
-
-
additional information
?
-
-
cytochrome c oxidase is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, the enzyme translocates protons across the membrane against this potential
-
-
-
additional information
?
-
Pseudomonas putida KT2240
Q88RM6
For all mutant strains, the NADH oxidation activity of membranes obtained from aerobic exponentially growing cultures is some higher than that of the wild-type strain (in the range of 1035% higher), inactivation of the Cbb3-1 terminal oxidase in a strain containing a wild-type ANR gene lead to a 46% decrease in cytochrome b and to a 57% decrease in cytochrome c
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heme
synthetic construct
-
reduction of dioxygen to water takes place at the heme a3-CuB binuclear center
heme
-
oxidation of heme a+a3 in cytochrome c oxidase of Prnp-/- mice is similar to that in Prnp+/+ mice
heme
P98002 and P08306
-
heme
-
binuclear heme center
heme
Q5SJ79, Q5SJ80, Q72H23
-
Heme a
-
located in subunit I
Heme a
-
2 heme a per complex of one subunit
Heme a
-
spectral studies
Heme a
-
chemical structure; spectral studies
Heme a
-
-
Heme a
-
-
Heme a
-
-
Heme a
-
located in subunit I
Heme a
-
acts as the electron transport prosthetic group of the enzyme
Heme a
synthetic construct
-
-
Heme a
-
CuA and heme a are in electronic equilibrium acting as a redox pair
Heme a
-
-
Heme a
-
-
Heme a3
-
located in subunit I
Heme a3
-
closely associated with CuB
Heme a3
-
located in subunit I
Heme a3
-
method for quantification of cytochrome c oxidase based upon the distinctive optical signal of the cyanide-ferroheme a3 compound in the visible region
Heme a3
-
located in subunit I
Heme a3
-
Trp-272 is the direct reductant either to the heme a3 oxoferryl species or to CuB2+
Heme a3
-
-
heme b
-
non-covalently bound
heme c
-
firmly bound
heme c
-
2 molecules in minimal structure unit composed of the three subunits
heme c
-
enzyme contains 3 heme c
heme c
-
located in subunit II
heme c
-
non-covalently bound
heme c
P98005
-
protoheme
-
1 molecule in minimal structure unit composed of the three subunits
protoheme
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
contains one Ca2+ per enzyme, tighly bound Ca2+ plays a structural role in the enzyme. Mutant enzyme D485A is active, binds to Ca2+ reversibly, and exhibits the red shift in the heme a absorption spectrum upon Ca2+ binding for both reduced and oxidized states of heme a. Sodium ions reverse the Ca2+-induced red shift of heme a and dramatically decrease the rate of Ca2+ binding to the mutant enzyme. With the mutant enzyme, 1 Ca2+ competes with 1 Na+ for the binding site
copper
-
Cox17p specifically binds Cu(I) at a molar copper content of 3.3 under redzuced conditions and significantly activates the mitochondrial. The Cu-Cox17p complex is maintained between pH values from 5.0 to 7.7. Cu is completely released from Cox17p at pH 8.0. The stringent selectivity of Cox17p for cipper is required for enzyme activation
copper
-
oxidation of copper in cytochrome c oxidase of Prnp-/- mice is similar to that in Prnp+/+ mice
copper
-
-
copper
-
-
copper
P98005
contains copper
copper
-
contains copper
Cu
-
CuA located in subunit II, binding of O2 and reduction; CuB located in subunit I, electron flow from ferrocytochrome c to binuclear center
Cu
-
discussion of Cu content
Cu
-
location in subunits
Cu
-
location in subunits; proposed third copper center, CuX, may result from impurities
Cu
-
location in subunits
Cu
-
2-3 Cu ions per complex of one subunit
Cu
-
structural interpretations of cytochrome c oxidase metal active sites by X-ray absorption spectroscopy, XAS, studies; X-ray absorption fine structure, EXAFS, studies
Cu
-
CuA contains a mononuclear Cu site with 2 cysteine sulfur and 2 imidazole nitrogen atoms as ligands
Cu
-
2 Cu atoms per enzyme molecule
Cu
-
CuA located in subunit II, binding of O2 and reduction; Cu-binding sites; CuB located in subunit I, electron flow from ferrocytochrome c to binuclear center
Cu
-
3 mol Cu per monomer
Cu
-
3 mol Cu per monomer
Cu
-
5 mol Cu per dimer
Cu
-
CuA may be coordinated by 2 cysteine ligands, CuA-protein coordination model
Cu
-
CuA-ligand structure
Cu
-
; models for metal binding
Cu
-
0.7 copper atoms in minimal structure unit composed of the three subunits
Cu
-
2 copper ions at the CuA site
Cu
-
CuA located in subunit II
Cu
-
0.96 mol Cu per mol of enzyme
Cu
-
2.8 - 3.8 nmol/mg protein
Cu
-
two atoms per molecule enzyme
Cu
synthetic construct
-
reduction of dioxygen to water takes place at the heme a3-CuB binuclear center
Cu
-
recombinant Cox19 binds 1 mol eq of Cu(I) per monomer. Cu(I) binding may be a transient property
Cu
-
contains copper
Cu2+
-
interaction of inhibitor nitric oxide is either with ferrous heme iron or oxidized copper, but not both simultaneously. The noncompetitive interaction with oxidized copper results in oxidation of NO to nitrite and behaves kinetically as if it has an apparent affinity of 28 nM
Cu2+
-
-
Cu2+
-
CuA and heme a are in electronic equilibrium acting as a redox pair. Trp-272 is the direct reductant either to the heme a3 oxoferryl species or to CuB2+
Cu2+
-
increases COX19 transcript levels
Fe
-
2 Fe per monomeric, catalytic unit of the enzyme, proton-induced X-ray emission study
Fe
-
3.0 iron in minimal structure unit composed of the three subunits
Fe
-
5.3 Fe atoms per enzyme complex
Fe
-
26.0 - 36.5 nmol/mg protein
Fe
-
two heme a and one protoheme per molecule enzyme
Fe
-
contains iron
Fe2+
-
interaction of inhibitor nitric oxide is either with ferrous heme iron or oxidized copper, but not both simultaneously. The affinity of NO for the oxygen-binding ferrous heme site is 0.2 nM
Fe2+
synthetic construct
-
-
Iron
-
contains iron
Mg
-
-
Mg
-
1 mol per monomeric functional unit
Mg
-
1 mol per monomeric functional unit
Mg
-
functional role of Mg and ATP binding site in association with subunit IV
Mg2+
P98005
contains Mg2+
Mn
-
when grown with 0.7 mM Mn2+ and 0.05 mM Mg2+, Mn2+ appears to be inserted into what is normally a Mg2+ site
Zn
-
function not known
Zn
-
1 Zn per 2 Fe, i.e. per functional cytochrome aa3 unit
Zn
-
one-half of Zn is tightly bound to subunit VI, 1 mol per functional unit, X-ray absorption fine structure, EXAFS, studies, Zn may play a structural role
Zn
-
1 Zn per monomeric catalytic unit, proton-induced X-ray emission studies
Zn
-
1 mol per 2 mol of heme a
additional information
-
all redox-active metal centers are contained in subunits I and II
additional information
-
enzyme does not contain Zn
additional information
-
enzyme does not contain Zn
additional information
-
variation of metal content with purification procedure
additional information
-
enzyme contains 5 redox-active metal sites
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-hydroxynonenal
-
time- and concentration-dependent inhibition of cytochrome c oxidase activity. Superoxide dismutase and catalase and the HO radical scavenger mannitol partially prevent inhibition of cytochrome c oxidase activity
aluminium phosphite
-
decrease in catalytic efficiency of active enzyme molecules on treatment with aluminium phosphide
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 peptides 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
-
ATP
-
the ATP-inhibition of CcO is only effective at very high ATP/ADP ratios (above 50) in the mitochondrial matrix or at low concentrations of ferrocytochrome c
azide
-
-
azide
-
heme-binding inhibitor, noncompetitive vs. O2 and cytochrome c
azide
-
0.08 mM, 50% inhibition
azide
-
1 mM, 50% inhibition of horse cytochrome c oxidation, 0.85 mM, 50% inhibition of horse cytochrome c oxidation in the presence of cardiolipin, 6.5 mM, 50% inhibition of Candida krusei cytochrome c oxidation, 1.5 mM, 50% inhibition of Nitrosomonas europaea cytochrome c oxidation
azide
-
0.08 mM, 50% inhibition
azide
-
0.1 mM, 50% inhibition
azide
-
0.014 mM, 50% inhibition of tuna cytochrome c oxidation
azide
-
0.11 mM, 50% inhibition, 10 mM, complete inhibition
azide
-
1 mM, 60% inhibition
azide
-
0.007 mM, 50% inhibition, 1 mM, complete inhibition
azide
-
uncompetitive inhibitor, inhibits the oxidase activity both in hypoxia and normoxia
bilirubin
-
0.05 mM serum unconjugated bilirubin rapidly and selectively inhibits cytochrome c oxidase activity. Pre-treatment of neurons with 0.05 mM glycoursodeoxycholic acid prior to exposure to serum unconjugated bilirubin prevents inhibition of cytrochrome c oxidase activity
Cl-
-
80 mM, complete inhibition
CN-
-
heme-binding inhibitor, noncompetitive vs. O2 and cytochrome c
CN-
-
0.0012 mM, complete inhibition
CN-
-
0.0001 mM, 50% inhibition
CN-
-
0.0012 mM, complete inhibition
CN-
-
0.13 mM, 50% inhibition of horse cytochrome c oxidation, 0.08 mM 50% inhibition of horse and Candida krusei cytochrome c oxidation in the presence of cardiolipin, 0.06 mM, 50% inhibition of Candida krusei cytochrome c oxidation, 0.05 mM, 50% inhibition of Nitrosomonas europaea cytochrome c oxidation
CN-
-
0.003 mM, 50% inhibition
CN-
-
0.001 mM, 50% inhibition
CN-
-
0.0013 mM, 50% inhibition
CN-
-
0.001 mM, 50% inhibition
CN-
-
0.004 mM, 50% inhibition of tuna cytochrome c oxidation
CN-
-
0.0013 mM, 50% inhibition, 1 mM, complete inhibition
CN-
-
0.1 mM, 96% inhibition
CN-
-
10 mM, complete inhibition
CN-
-
0.0005 mM, 50% inhibition
CN-
-
0.001 mM, 59% inhibition
CN-
-
0.012 mM, 50% inhibition
CN-
-
0.02 mM, inhibition of peroxynitrite reduction
CN-
-
mixed inhibitor
CO
-
competitive vs. O2
CO
-
competitive vs. O2
CO
-
competitive vs. O2
CO
-
competitive vs. O2
CO
-
competitive and reversible
CO
-
significantly decreases myocardial CcOX activity. CcOX I protein levels significantly decrease following CO exposure while enzyme turnover number and CcOX I mRNA levels remain unchanged. Decreased CcOX activity following CO inhalation is likely due to decreased heme aa3 and CcOX subunit I content
CO
-
inhibits cytochrome c oxidase activity by 50%. Acts via inhibition of cytochrome c oxidase leading to the generation of low levels of reactive oxygen species that in turn mediate subsequent adaptive signaling. CO inhibits cytochrome c oxidase, while maintaining cellular ATP levels and increasing mitochondrial membrane potential
CO
-
competitive inhibitor
Cu2+
-
inhibition of enzyme by amyloid beta depends completely on presence of divalent Cu2+, but not Cu+
cyanide
-
-
cyanide
-
Pseudomonas fluorescens strain CHA0 can kill Odontotermes obesus by inhibiting cytochrome c oxidase of the termite respiratory chain with the pseudomonad metabolite cyanide after a 2 h incubation period
Dicyclohexylcarbodiimide
-
-
Dicyclohexylcarbodiimide
-
inhibition of redox-linked proton translocation
diethylenetriamine-NONOate
-
-
ethylene glycol
-
inhibits by reducing electron flow between cytochrome a and cytochrome a3
ferricytochrome c
-
-
Hg2+
-
cytochrome c oxidase activities of strains AP19-3 and ATCC 23270 are completely inhibited by 0.001 mM and 0.005 mM. Strain MON-1 is inhibited 33% by 0.005 mM, and 70% by 0.010 mM
High ionic strength
-
above 200 mM KCl
-
HIV-1 neurotoxin trans activator of transcription protein
-
inhibits the electron transport chain in a concentration-dependent manner. A concentration of 5 ng/ml, 50 ng/ml, and 10 microg/ml inhibit activity to 84, 47, and 35% of control, respectively
-
KCl
-
20 mM, 50% inhibition
KCl
-
50 mM, 50% inhibition
KCN
-
1 mM results in a sustained 50% loss of activity following 24, 48 and 72 h of culture
KCN
-
1 mM completely inhibits
KCN
Q88RM6
1 mM inhibits all terminal oxidases excepting the CIO quinol oxidase and lead to reduced NADH oxidation between 2.5- and 4fold
Lithium diiodosalicylate
-
-
N,N-Dimethyllauryl amine oxide
-
-
N3-
-
non-competitive inhibitor
NaCN
-
1 mM completely inhibits mercury volatilization activities with reduced cytochrome c and 2,3,5,6-tetramethyl-p-phenylendiamine in strain MON-1
NaN3
-
reduces COx activity in homogenates of the cortex and hippocampus by 40% and 37% respectively, 4 weeks after pump implantation
NaN3
-
-
NH2OH
-
3 mM, 80% inhibition
nitric oxide
-
competitive and reversible. Nanomolar levels inhibit the enzyme by competing with oxygen at the enzymes heme-copper active site. This raises the Km for cellular respiration into the physiological range
nitric oxide
-
partial inhibition of cytochrome-c oxidase by nitric oxide leads to an accumulation of reduced cytochrome c and to an increase in electron flux through the enzyme population not inhibited by nitric oxide
nitric oxide
-
steady-state and kinetic modeling of inhibition. NO interacts with either ferrous heme iron or oxidized copper, but not both simultaneously. The affinity of NO for the oxygen-binding ferrous heme site is 0.2 nM
nitric oxide
-
nitric oxide generated from NaNO2 decreases cellular oxygen consumption and inhibits CcOX activity
nitric oxide
-
nitric oxide that is not inactivated inhibits the cytochrome c oxidase, reducing the enzyme and lowering O2 consumption
NO
-
competitive vs. O2
NO
synthetic construct
-
simple dynamic steady-state non-equilibrium model. Binding to the oxidase is always proportional to the degree of inhibition of oxygen consumption. Primary effect of NO binding to the oxidised enzyme is to convert NO to nitrite, rather than to inhibit enzyme activity
NO
-
irreversibly inhibits in a reverse oxygen concentration-dependent manner. COX activity is decreased from 51.3% at 0.2 mM and to 3.8% at 0.025 mM. Inhibition is dramatically protected by a peroxynitrite scavenger, which is formed from the reaction of NO with cytochrome oxidase at low oxygen concentration, and that is involved in irreversible cytochrome oxidase inactivation. Nitroxyl anion scavenger potently protects the irreversible inhibition, whereas a superoxide dismutase does not provide protective effect, suggesting that the peroxynitrite is formed from nitroxyl anion rather than the reaction of NO with superoxide
NO
-
inhibits cytochrome oxidase in competition with oxygen. Hypoxia (2% O2) markedly inhibits cytochrome oxidase activity (relative to normoxia), and N-4S-4-amino-5-2-aminoethylaminopentyl-N'-nitroguanidine reverses this inhibition in the presence of hypoxia, but has no effect in normoxia
NO
-
increased NO production after traumatic brain injury triggers inhibition of CcO. Traumatic brain injury leads to CcO inhibition and dramatically decreased ATP levels in brain cortex. CcO inhibition can be partially restored by application of iNOS antisense oligonucleotides prior to traumatic brain injury, which leads to a normalization of ATP levels similar to the controls
NO
-
competitive inhibitor
NO2-
-
competitive inhibitor
Nonionic detergents
-
-
-
peroxynitrite
-
0.1 mM, complete inhibition
phosphate
-
more than 15 mM
phosphate
-
-
phosphate
-
-
phosphate
-
not with yeast cytochrome c
phosphate
-
more than 10 mM
phosphate
-
more than 70 mM
phosphate
-
more than 10 mM
poly-L-lysine
-
complete inhibition of horse and Candida krusei cytochrome c oxidation with 0.0001 mM and 0.002 mM poly-L-lysine, respectively
potassium cyanide
-
2 mM inhibits electron flow from complex IV to oxygen
potassium cyanide
-
-
potassium cyanide
-
-
potassium cyanide
-
0.25 mM potassium cyanide completely and reversibly inhibits both the electron and proton transport function of COX, the addition of 60 mM pyruvate induces the maximal recovery of both parameters to 60-80% of the original values. Low KCN concentrations of up to 0.005 mM lead to a profound, 30fold decrease of COX affinity for oxygen
potassium cyanide
-
cyanide binds to the binuclear heme center of cytochrome c oxidase, complete inhibition at 0.02 mM, pretreatment with NaNO2 reverses potassium cyanide-mediated inhibition of CcOX activity
Salicyl aldoxime
-
-
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
-
5 mM inhibits electron flow from complex IV to oxygen
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
Sodium deoxycholate
-
-
Sulfide
-
-
Sulfide
-
heme-binding inhibitor, noncompetitive vs. O2 and cytochrome c
theophylline
-
at therapeutic concentrations used for asthma relief, theophylline causes inhibition of the lung enzyme and decreases cellular ATP levels, suggesting a mechanism for its clinical action
trans-[RuCl2(3,4-pyridinedicarboxylic acid)4]Cl
-
inhibits COX activity in kidney
-
trans-[RuCl2(3-pyridinecarboxylic acid)4]
-
inhibits COX activity in heart and kidney
trans-[RuCl2(4-pyridinecarboxylic acid)4]
-
inhibits COX activity in hippocampus, heart, liver and kidney
Triton X-100
-
0.3%, 50% inhibition
Triton X-100
-
-
Tumor necrosis factor alpha
-
leads to an ca. 60% reduction in CcO activity in hepatocyte homogenates. Shows no direct effect on CcO activity using purified CcO. CcO isolated after tumor necrosis factor alpha treatment shows tyrosine phosphorylation on CcO catalytic subunit I and is ca. 50 and 70% inhibited at high cytochrome c concentrations in the presence of allosteric activator ADP and inhibitor ATP, respectively
-
Tumor necrosis factor alpha
-
leads to reduction in CcO activity in hepatocyte homogenates. Shows no direct effect on CcO activity using isolated mitochondria CcO
-
Tween 20
-
0.5%, 40% inhibition
Tween 80
-
0.5% 60% inhibition
Zn2+
-
reaction of enzyme in detergent solution and reconstituted in phospholipid vesicles. At concentrations of Zn2+ below 0.25 mM at the outside of the vesicles, transistion rates between intermediates is not altered. Zn2+ ions bind on both sides of the enzyme and binding at the proton output side selectively impairs proton release during the transition of peroxy intermediate to oxo-ferryl intermediate
Zn2+
-
tetrahedral coordination of Zn2+ with two N-histidine imidazoles, one N-histidine imidazol or N-lysine and one O-COOH, possibly located at the entry site ogf the proton conducting D pathway; tetrahedral coordination site(s) for Zn2+ with two N-histidine imidazoles, one N-histidine imidazol or N-lysine and one O-COOH (glutamate or aspartate), possibly located at the entry site of the proton conducting D pathway in the oxidase and involved in inhibition of the oxygen reduction catalysis and proton pumping by internally trapped zinc. Presence of ZnCl2 during liposome reconstitution of cytochrome c oxidase has no effect on the sidedness of the incorporated COX, neither increases the residual amount of soluble COX
Zn2+
-
the Glu-101/His-96 site of subunit II as the site of metal binding inhibits the uptake of protons into the K pathway. Subunit III contributes to zinc binding and/or inhibition of the D pathway
miltefosine
-
inhibits in a dose-dependent manner. CcO appears to be an important target, as inhibition by this drug runs parallel to the alteration of processes such as O2 consumption and mitochondrial membrane potential, as well as the drop in ATP levels
additional information
-
not inhibited by Triton X-100 up to a concentration of 2%
-
additional information
-
cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity
-
additional information
-
high percentage levels of mutated mitochondrial DNA are associated with a dramatic reduction in wild-type levels and COX deficiency. For the m.3243ArG mutation, a superabundance of wild-type mitochondrial DNA is found in many muscle-fiber sections with negligible COX activity
-
additional information
-
after 30 min of ischemia and 120 min of reperfusion, total COI levels decrease in the left ventricular regions at risk by 72%. Subunit Va is also downregulated by 42% following prolonged ischemia-reperfusion in the left ventricular regions at risk. Cardiac ischemic preconditioning administered before ischemia-reperfusion reduces the loss of COI approximately 30% and prevents COVa losses completely. No losses in subunits Vb and VIIa following ischemia-reperfusion alone, but significant losses occur when cardiac ischemic preconditioning is administered before prolonged ischemia-reperfusion. Delivery of a cell-permeable PKC-epsilon translocation inhibitor to isolated rat hearts before prolonged ischemia-reperfusion dramatically increases COI loss
-
additional information
-
knocked down frataxin in oligodendroglioma cells using siRNA produces significant defects in the activity of cytochrome oxidase. Exogenous hemin produces a significant rescue of cytochrome oxidase activity
-
additional information
-
CcO immobilized on a metal film
-
additional information
Q88RM6
Inactivation of the Aa3 oxidase lead to a 50% reduction in N,N,N',N'-tetramethyl-1,4-benzenediamine (TMPD)-dependent oxidase activity (electron donor specific for cytochrome c-dependent oxidases). Lack of the Cbb3-2 oxidase lead to 65% reduction.; In cells growing exponentially under high oxygen tension (100% air saturation), the absence of ANR lead to a 20fold decrease in mRNA levels of the Cbb3-1 oxidase gene, a decrease that is 10-fold lower than that observed in cells growing exponentially in shaken flasks, and 35-fold lower than in cells entering the stationary phase. When cells are grown under limiting oxygen supply (40% air saturation), the absence of ANR lead to a over 500fold decrease in the mRNA levels of the Cbb3-1 oxidase gene; Under aerobic conditions, inactivation of transcriptional activator gene ANR lead to a significant decrease (more than 230fold) of the mRNA corresponding to the Cbb3-1 oxidase, but have little effect on the other analysed terminal oxidases Cbb3-2 and Aa3.
-
additional information
-
CCO activity, the content of the mitochondrial-encoded CCO subunit 1 (COX1), and the content of the nuclear-encoded subunit COX4 in cardiac mitochondria are reduced in 21-d-old offspring of Cu-deficient dams. COX1 content is normal in 21-d-old cross-fostered offspring of Cu-deficient dams, but CCO activity and COX4 are reduced
-
additional information
-
incubation of the isolated enzyme with protein kinase A, cAMP, and ATP results in serine and threonine phosphorylation of CcO subunit I, which is correlated with sigmoidal inhibition kinetics in the presence of ATP
-
additional information
-
rapid isolation of mitochondria from rat heart in the presence of various protein phosphatase inhibitors (in the presence of 25 mM NaF, 5 mM sodium vanadate, 10 nM okadaic acid, 2 mM EGTA, and 0.2% bovine serum albumin) results in CcO kinetics with allosteric ATP-inhibition and phosphorylation of subunit I at serine, threonine, and tyrosine
-
additional information
-
enzyme activity decreases only at the late stage of diabetes which is not normalized by insulin treatment. Activity at room temperature (25C) as well as at physiological temperature (37C) is not affected by the diabetic state. At the late stage of diabetes the activity at 37C decreases by 22%
-
additional information
-
ethanol withdrawal decreases the activity of total COX, COX I, and COX IV. Estrogen treatment (17beta-estradiol) prevents the effects of withdrawal on the activities of total COX and COX IV but not COX I. Neither withdrawal nor 17beta-estradiol alter the protein levels of the subunits
-
additional information
-
15 min of global ischemia leads to the inhibition of COXI synthesis to 56% of control. After 1, 3 and 24 hours of reperfusion, COXI synthesis is inhibited to 46, 50 and 72% of control, respectively. Extent COXIII and COXII/ATPase6 synthesis inhibition is comparable to the extent of COXI synthesis inhibition. No significant changes in COXI mRNA and in both COXI and COXII protein level after ischemia, thus ischemia-reperfusion affects directly mitochondrial translation machinery. Ischemia in duration of 15 min and consequent 1, 3 and 24 hours of reperfusion leads to the inhibition of COX activity to 90.3, 80.3, 81.9 and 83.5% of control, respectively
-
additional information
-
import of COX19 is not inhibited by the ionophore valinomycin indicating that an electrical membrane potential is not required
-
additional information
-
is competitively inhibited early in sepsis and progresses, becoming noncompetitive during the late phase. Exogenous cytochrome c can overcome this myocardial CcOX competitive inhibition. Cecal ligation and puncture inhibit CcOX at 48 h in saline-injected mice. However, cytochrome c injection abrogates this inhibition and restores CcOX kinetic activity to sham values at 48 h
-
additional information
-
rats exposed to a GSM signal at 6W/Kg show decreased CO activity in some areas of the prefrontal and frontal cortex (infralimbic cortex, prelimbic cortex, primary motor cortex, secondary motor cortex, anterior cingulate cortex areas 1 and 2), the septum (dorsal and ventral parts of the lateral septal nucleus), the hippocampus (dorsal field CA1, CA2 and CA3 of the hippocampus and dental gyrus) and the posterior cortex (retrosplenial agranular cortex, primary and secondary visual cortex, perirhinal cortex and lateral entorhinal cortex). Exposure to GSM at 1.5W/Kg does not affect brain activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-Amino-1,2,4-triazole
-
-
asolectin
-
-
-
asolectin
-
20-30% more activity in the presence of asolectin
-
Caffeine
P17665
increases Cox7c mRNA expression in the male striatum. Cox7c is up-regulated in the striatum of male but not female mice after receiving a single dose of caffeine. Cox1 and Cox4 are also stimulated by caffeine in a male-specific fashion. A2AR-specific agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine counteracts the elevation of Cox expression and activity by caffeine
Caffeine
-
increases Cox7c mRNA expression in PC-12 cells. This occurrs at the level of transcription and is mediated by a segment of the Cox7c promoter
cardiolipin
-
stimulation with non-physiological electron donors
cardiolipin
-
stimulation of reaction with horse ferrocytochrome c, reactivity with cytochrome c550 is not affected
cardiolipin
-
approx. 10fold stimulation
cardiolipin
-
activation if horse heart or Candida krusei cytchrome c are used as electron donors
cardiolipin
-
-
Cox17p
-
Cox17p specifically binds Cu(I) at a molar copper content of 3.3 under redzuced conditions and significantly activates the mitochondrial. The Cu-Cox17p complex is maintained between pH values from 5.0 to 7.7. Cu is completely released from Cox17p at pH 8.0. The stringent selectivity of Cox17p for cipper is required for enzyme activation
-
Cox17p
-
activation may not be essential to the progress of embryogenesis before gastrulation
-
n-octylglucoside
-
0.1%, 2.7fold stimulation
n-octylglucoside
-
0.05%, 6fold stimulation
NO
-
geminates recombination in mitochondrial CcO. Can accommodate only one NO molecule in its active site
NO
-
is able to bind two NO molecules in its active site. NO is expected to have only a marginal regulatory role at the level of CcO aa
phosphatidylcholine
-
2.7fold activation of horse heart cytochrome c mediated reaction, 3fold activation of Candida krusei cytchrome c mediated reaction
phosphatidylcholine
-
3fold activation
phosphatidylethanolamine
-
more than 3fold activation
phosphatidylinositol
-
2.1fold activation of horse heart cytochrome c mediated reaction, 2.4fold activation of Candida krusei cytchrome c mediated reaction
phosphatidylserine
-
7.2fold activation of horse heart cytochrome c mediated reaction, 4.7fold activation of Candida krusei cytchrome c mediated reaction
Phospholipid
-
activation
Phospholipid
-
activation
Phospholipid
-
10fold activation
Phospholipid
-
100% stimulation
Phospholipid
-
activation
poly-L-lysine
-
strong activation of Nitrosomonas europaea cytochrome c oxidation
pyrroloquinoline quinone
-
PQQ
salicylic acid
-
produces a slight and transient increase in transcript levels of COX19
SCH58261
P17665
A2AR antagonist, which stimulates Cox expression and activity
siRNA
-
knockdown of Cox7c expression in PC-12 cells blunts Cox activity, which is counteracted by caffeine treatment
-
Sodium cholate
-
0.5%, activation if horse heart or Candida krusei cytchrome c are used as electron donors
sodium nitroprusside
-
produces a several fold increase in COX19 expression after 4 h of treatment, but transcript levels return to normal values after higher incubation times
sodiumdodecylsulfate
-
0.01%, strong activation if horse heart or Candida krusei cytchrome c are used as electron donors
Surf1
-
biogenesis of mitochondrial cytochrome c oxidase relies on a large number of assembly factors, among them the transmembrane protein Surf1
-
trans-[RuCl2(3,4-pyridinedicarboxylic acid)4]Cl
-
increases COX activity in hippocampus, striatum and cerebral cortex
-
trans-[RuCl2(3,5-pyridinedicarboxylic acid)4]
-
increases COX activity in hippocampus, striatum, cerebral cortex and kidney
Triton X-100
-
0.5%, 10% activation
Tween 80
-
3.5%, 1.8fold stimulation
Tween 80
-
-
Tween 80
-
0.5%, 533% stimulation
Tween 80
-
1% slight stimulation
Tween 80
-
-
Tween-20
-
-
Tween-20
-
the CcO activity of rat liver and heart mitochondria in the presence of 5 mM ADP increases with increasing Tween-20 concentrations. With rat liver mitochondria almost no CcO activity is found in the absence of Tween-20 in contrast to heart mitochondria, where about 50% of maximal activity is measured. Maximal activity rates are measured between 0.5% and 2% (v/v) Tween-20
Insulin
-
insulin treatment at early stage of diabetes (1-week diabetic animals) results in hyper-stimulation, but it is ineffective in restoring the activity in 1-month diabetic animals
-
additional information
-
no activation with phospholipids
-
additional information
-
no activation with Tween 20, Triton X-100 or phosphatidylcholin
-
additional information
-
mechanism of antibody-induced stimulation of COX electron transfer activity. Subunit III is conformationally linked to the redox centers in subunit I of the enzyme. Antibody binding to subunit III perturbs the interaction of subunit III with subunit I to cause an increase in electrin transfer rate
-
additional information
-
activity of cytochrome-c oxidase from heart is 2-7fold increased when the membrane integrity is disrupted by hypotonic swelling, freeze-thawing, or a detergent
-
additional information
-
overexpression of subunit Vb increases COX activity and decreases reactive oxygen species production in wild-type HeLa-20 cells, along with some increase in tolerance to hyperoxia
-
additional information
-
haloperidol, clozapine, olanzapine, or aripiprazole do not alter COX
-
additional information
-
segments of human skeletal muscle fibers harboring two pathogenic mitochondrial DNA mutations retain normal COX activity by maintaining a minimum amount of wild-type mitochondrial DNA
-
additional information
-
ischemic preconditioning administered before prolonged ischemia-reperfusion induces a 1.9fold increase in coimmunoprecipitation of cytochrome oxidase subunit IV, with anti-PKC-epsilon antisera and a 2fold enhancement of cytochrome-c oxidase activity. Intact mitochondria show virtually no cytochrome-c oxidase activity, unless they are permeablized with n-dodecyl-beta,D-maltoside
-
additional information
-
arachidonic acid, cholic acid and CHAPS have no effect on the activity of wild-type CcO
-
additional information
-
decreasing pH from 8.0 to 6.4 is accompanied by a 5fold increase of cytochrome oxidase activity
-
additional information
-
CcO immobilized on a metal film can be activated by cytochrome c oxidation/reduction
-
additional information
-
tridentate cross-linked histidine-phenol Cu(II) ether and ester complexes as chemical analogs of the active site
-
additional information
synthetic construct
-
synthetic models of the active site of cytochrome c oxidase [(LN4-OH)CuI-FeII(TMP)]+ and [(LN3-OH)CuI-FeII(TMP)]+
-
additional information
-
chronic high-frequency stimulation of the subthalamic nucleus increases COI mRNA expression, suggesting global activation of globus pallidus internalis neurons
-
additional information
-
protein kinase C epsilon activates under hypoxic conditions. CytCOx activity is increased by 5fold after hypoxia. Under normoxic conditions, in whole lenses, there is only a weak interaction between protein kinase C epsilon and CytCOx
-
additional information
-
after administering NaN3, chronic treatment with ladostigil prevents the decrease in choline acetyltransferase in the diagonal band, the compensatory increase in synaptic plasticity and transferrin receptors and the memory deficits without restoring COx activity
-
additional information
-
overexpression of the NF-YA/B/C transcription complex in SURF1-deficient fibroblasts from an Leighs syndrome patient efficiently rescues their COX deficiency
-
additional information
-
overexpression of Hap4p, the catalytic subunit of the CCAAT binding transcriptional activator Hap2/3/4/5p complex, suppresses the respiratory defect of yeast shy1 mutants by increasing the expression of nuclear-encoded COX subunits that interact with the mitochondrially encoded Cox1p
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00002
cytochrome c
-
biphasic kinetic with 2 different Km values
0.00005
cytochrome c
-
high-affinity Km
0.00006
cytochrome c
-
biphasic kinetic, high-affinity phase Km
0.00012
cytochrome c
-
heart enzyme, high affinity Km, in the presence of 0.04% deoxycholate and 0.04% lipid
0.00016
cytochrome c
-
liver enzyme, high affinity Km, in the presence of 0.04% deoxycholate and 0.04% lipid
0.00071
cytochrome c
-
heart enzyme, low affinity Km, in the presence of 0.04% deoxycholate and 0.04% lipid
0.00126
cytochrome c
-
2 Km values for horse heart, Neurospora crassa, Saccharomyces cerevisiea and Candida krusei cytochrome c
0.0013
cytochrome c
-
horse heart cytochrome c, chymotrypsin treated enzyme
0.00132
cytochrome c
-
horse heart cytochrome c, high-affinity Km, 30 mM ionic strength
0.0014
cytochrome c
-
horse heart cytochrome c
0.00148
cytochrome c
-
liver enzyme, low affinity Km, in the presence of 0.04% deoxycholate and 0.04% lipid
0.0017
cytochrome c
-
horse cytochrome c, presence of cardiolipin
0.0017
cytochrome c
-
horse heart cytochrome c, in the presence of 0.1% Triton X-100 and 2 mg/ml asolectin, chymotrypsin treated enzyme
0.0018
cytochrome c
-
horse cytochrome c, in the presence of cardiolipin
0.002
cytochrome c
-
-
0.002
cytochrome c
-
yeast cytochrome c
0.002
cytochrome c
-
low-affinity Km
0.002
cytochrome c
-
Saccharomyces cerevisiae cytochrome c
0.0021
cytochrome c
-
horse heart cytochrome c, in the presence of 0.1% Triton X-100 and 2 mg/ml asolectin
0.0036
cytochrome c
-
enzyme from swayback-diseased liver, low-affinity Km
0.0037
cytochrome c
-
-
0.0037
cytochrome c
-
Candida krusei cytochrome c
0.0037
cytochrome c
-
Candida krusei cytochrome c, in the presence of cardiolipin
0.0038
cytochrome c
-
horse cytochrome c, in the presence of cardiolipin
0.004
cytochrome c
-
biphasic kinetic with 2 different Km values
0.004
cytochrome c
-
horse cytochrome c, in dodecylmaltoside
0.0042
cytochrome c
-
biphasic kinetic, low-affinity phase Km
0.0045
cytochrome c
-
yeast cytochrome c
0.0047
cytochrome c
-
Candida krusei cytochrome c
0.0047
cytochrome c
-
enzyme from swayback-diseased brain, low-affinity Km
0.0055
cytochrome c
-
horse heart cytochrome c
0.0058
cytochrome c
-
enzyme from normal liver, high-affinity Km
0.006 - 0.077
cytochrome c
-
dependency on pH, phosphate and K+ concentration
0.0067
cytochrome c
-
-
0.0067
cytochrome c
-
Saccharomyces cerevisiae cytochrome c
0.0067
cytochrome c
-
enzyme from normal liver, low-affinity Km
0.008
cytochrome c
-
low affinity Km, liver enzyme at 27 mM ionic strength
0.0081
cytochrome c
-
horse cytochrome c
0.0087
cytochrome c
-
Candida krusei cytochrome c
0.01 - 0.015
cytochrome c
-
-
0.01
cytochrome c
-
yeast cytochrome c, approx. value
0.011
cytochrome c
-
horse cytochrome c
0.011
cytochrome c
-
horse heart cytochrome c
0.011
cytochrome c
-
low affinity Km, muscle enzyme at 27 mM ionic strength
0.011
cytochrome c
-
-
0.011
cytochrome c
-
-
0.012
cytochrome c
-
horse cytochrome c, absence of cardiolipin
0.012
cytochrome c
-
low affinity Km, kidney enzyme at 27 mM ionic strength
0.012
cytochrome c
-
horse heart cytochrome c
0.012
cytochrome c
-
enzyme from normal brain, low-affinity Km; enzyme from swayback-diseased liver, high-affinity Km
0.013
cytochrome c
-
Thermus thermophilus cytochrome c
0.015
cytochrome c
-
horse heart cytochrome c
0.015
cytochrome c
-
low affinity Km, heart enzyme at 27 mM ionic strength
0.015
cytochrome c
-
yeast cytochrome c, in the presence of 100 mM KCl
0.0153
cytochrome c
-
horse heart cytochrome c, 100 mM ionic strength
0.016
cytochrome c
-
horse heart cytochrome c, in the presence of 50 mM KCl
0.016
cytochrome c
-
Candida krusei cytochrome c
0.017
cytochrome c
-
kidney enzyme, 226 mM ionic strength
0.019
cytochrome c
-
Candida krusei cytochrome c
0.019
cytochrome c
-
oxidation of horse cytochrome c
0.022
cytochrome c
-
liver enzyme, 226 mM ionic strength
0.023
cytochrome c
-
heart enzyme, 226 mM ionic strength
0.024
cytochrome c
-
horse cytochrome c
0.025
cytochrome c
-
muscle enzyme, 226 mM ionic strength
0.025
cytochrome c
-
adult heart enzyme
0.026
cytochrome c
-
oxidation of bovine or yeast cytochrome c
0.027
cytochrome c
-
Candida krusei cytochrome c
0.029
cytochrome c
-
Saccharomyces oviformis cytochrome c
0.031
cytochrome c
-
Nitrosomonas europaea cytochrome c
0.032 - 0.044
cytochrome c
-
-
0.038
cytochrome c
-
fetal heart enzyme
0.041
cytochrome c
-
horse cytochrome c
0.05
cytochrome c
-
horse and native cytochrome c
0.053
cytochrome c
-
tuna cytochrome c
0.055
cytochrome c
-
enzyme from normal brain, high-affinity Km
0.06
cytochrome c
-
-
0.067
cytochrome c
-
Saccharomyces cerevisiae cytochrome c
0.074
cytochrome c
-
Candida krusei cytochrome c
0.11
cytochrome c
-
horse cytochrome c
0.12
cytochrome c
-
cow cytochrome c
0.13
cytochrome c
-
horse heart cytochrome c
0.13
cytochrome c
-
from horse heart, bacterial enzyme
0.13
cytochrome c
-
hose cytochrome c
0.13
cytochrome c
-
horse heart cytochrome c, low-affinity Km, 30 mM ionic strength
0.067
cytochrome c-551
-
from thermophilic bacterium PS3, bacterial enzyme
-
0.011
cytochrome c-552
-
from Thermus thermophilus, bacterial enzyme
-
0.0065
cytochrome c549
-
-
-
0.003
cytochrome c550
-
Magnetospirillum magnetotacticum cytochrome c550
0.008
cytochrome c550
-
-
0.067
cytochrome c551
-
cytochrome c551 from thermophilic bacterium PS3
-
0.002 - 0.003
cytochrome c552
-
-
-
0.0022
cytochrome c552
-
-
-
0.0043
cytochrome c552
-
-
-
0.0093
cytochrome c552
-
at pH 3.5
-
0.011
cytochrome c552
-
cytochrome c552 from Thermus thermophilus
-
0.016
cytochrome c552
-
-
-
0.018
cytochrome c552
-
-
-
0.0009
cytochrome c553
-
-
-
0.009
Ferrocytochrome
-
reduced horse heart cytochrome
0.00005
ferrocytochrome c
-
high affinity Km, kidney, heart, and muscle enzyme, at 27 mM ionic strength
0.00007
ferrocytochrome c
-
high affinity Km, liver enzyme, at 27 mM ionic strength
0.037
ferrocytochrome c
-
following sham exposure
0.041
ferrocytochrome c
-
following CO exposure
0.11
ferrocytochrome c
-
horse cytochrome c
0.23
N,N,N',N'-tetramethyl-1,4-phenylendiamine dihydrochloride
-
-
0.27
N,N,N',N'-tetramethyl-1,4-phenylendiamine dihydrochloride
-
-
2
N,N,N',N'-tetramethyl-p-phenylendiamine
-
-
0.86
N,N,N',N'-tetramethyl-p-phenylenediamine
-
-
0.09
o-Dianisidine
-
at 1 mM H2O2
0.00004
O2
-
-
0.001
O2
-
-
0.000023
reduced cytochrome c551
-
mutant enzyme E116Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000026
reduced cytochrome c551
-
wild type enzyme, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000035
reduced cytochrome c551
-
mutant enzyme E84Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000044
reduced cytochrome c551
-
mutant enzyme D49N, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000059
reduced cytochrome c551
-
mutant enzyme E66Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000063
reduced cytochrome c551
-
mutant enzyme E139Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000074
reduced cytochrome c551
-
mutant enzyme E68Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.0001
reduced cytochrome c551
-
mutant enzyme E64Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.000154
reduced cytochrome c551
-
mutant enzyme D99N, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
0.024
ferrocytochrome c550
-
-
-
additional information
additional information
-
enzyme exhibits positive cooperativity at low ionic strength, increasing the KCl concentration to 25 mM causes loss of cooperativity
-
additional information
additional information
-
comparison of high and low affinity Km values at low ionic strength with Rhodobacter spaeroides and horse cytochrome c of wild-type and various mutants
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.57
cytochrome c
-
horse cytochrome c
1.6
cytochrome c
-
Candida krusei cytochrome c
1.8
cytochrome c
-
Nitrosomonaseuropaea cytochrome c
2.08 - 2.58
cytochrome c
-
-
3.88
cytochrome c
-
horse cytochrome c
4 - 5
cytochrome c
-
Saccharomyces cerevisiae cytochrome c, in the presence of 0.05% laurylmaltoside
5 - 7
cytochrome c
-
Saccharomyces cerevisiae cytochrome c, in the presence of asolectin
6
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, W143A mutant enzyme
8 - 12
cytochrome c
-
in the presence of 0.1% dodecyl-beta-D-maltoside
8.33
cytochrome c
-
Candida krusei cytochrome c
9.38
cytochrome c
-
horse heart cytochrome c
11 - 30
cytochrome c
-
oxidation of horse heart cytochrome c
13.3 - 16
cytochrome c
-
enzyme reconstituted into asolectin liposomes
14
cytochrome c
-
Candida krusei cytochrome c, in the presence of cardiolipin
20
cytochrome c
-
Thiobacillus novellus cytochrome c, 12.5 mM phosphate at pH 5.5 and 20C
20
cytochrome c
-
horse cytochrome c, W143A mutant enzyme; Rhodobacter sphaeroides cytochrome c, W143F mutant enzyme
20
cytochrome c
-
R54M mutant enzyme
24
cytochrome c
-
Candida krusei cytochrome c
30 - 600
cytochrome c
-
-
30
cytochrome c
-
high-affinity reaction
32
cytochrome c
-
horse cytochrome c
32
cytochrome c
-
horse cytochrome c, in the presence of cardiolipin
36
cytochrome c
-
oxidation of horse heart cytochrome c
40
cytochrome c
-
-
40
cytochrome c
-
horse cytochrome c, W143F mutant enzyme
45.8
cytochrome c
-
Candida krusei cytochrome c, 30 mM phosphate at pH 5.5 and 20C
50 - 100
cytochrome c
-
soluble enzyme, higher values for particulate enzyme
50
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, D229N mutant enzyme
53
cytochrome c
-
Thermus thermophilus cytochrome c
54
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, D195Q mutant enzyme
66
cytochrome c
-
horse heart cytochrome c
80
cytochrome c
-
low-affinity reaction
80
cytochrome c
-
horse cytochrome c
90
cytochrome c
-
horse-heart cytochrome c
90
cytochrome c
-
cow cytochrome c
91
cytochrome c
-
-
100
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, E157Q and E254A mutant enzyme
111
cytochrome c
-
Crithidia fasciculata cytochrome c, very low turnover numbers with human, yeast, rat, horse, and bovine cytochrome c
120
cytochrome c
-
fetal heart enzyme
133
cytochrome c
-
-
158
cytochrome c
-
horse cytochrome c
160
cytochrome c
-
Saccharomyces oviformis cytochrome c
180
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, D214N mutant enzyme
187
cytochrome c
-
horse heart cytochrome c
200
cytochrome c
-
adult heart enzyme
220
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, D151N/E152Q mutant enzyme
230
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, E148Q mutant enzyme
260
cytochrome c
-
tuna cytochrome c
260
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, D188N/E189Q mutant enzyme
270
cytochrome c
-
Rhodobacter sphaeroides cytochrome c, wild-type enzyme
290
cytochrome c
-
Candida krusei cytochrome c
290
cytochrome c
-
wild-type enzyme, horse cytochrome c, 155 mM ionic strength
300
cytochrome c
-
horse heart cytochrome c
300
cytochrome c
-
-
300
cytochrome c
-
horse heart cytochrome c
336
cytochrome c
-
horse cytochrome c, in the presence of cardiolipin
350
cytochrome c
-
muscle enzyme
360
cytochrome c
-
muscle enzyme
380
cytochrome c
-
heart enzyme
400 - 500
cytochrome c
-
-
400
cytochrome c
-
horse cytochrome c, D214N and D229N mutant enzyme
410
cytochrome c
-
muscle enzyme
500
cytochrome c
-
enzyme from kidney, photometric assay
520
cytochrome c
-
enzyme from diaphragm, photometric assay
535
cytochrome c
-
purified COV
540
cytochrome c
-
enzyme from liver, photometric assay
550
cytochrome c
-
enzyme from heart, photometric assay
550
cytochrome c
-
reconstituted recombinant D407C mutant enzyme
590
cytochrome c
-
wild-type enzyme, horse cytochrome c, 5 mM ionic strength
600
cytochrome c
-
horse cytochrome c, E157Q and E254Amutant enzyme
650
cytochrome c
-
recombinant D407C mutant enzyme
700
cytochrome c
-
reconstituted recombinant D407A mutant enzyme; reconstituted recombinant D407N mutant enzyme
708
cytochrome c
-
unpurified COV
980
cytochrome c
-
wild-type, D188N/E189Q and D151N/E152Q mutant enzyme, horse cytochrome c, 75 mM ionic strength
1000
cytochrome c
-
-
1100
cytochrome c
-
recombinant D407A mutant enzyme
1100
cytochrome c
-
horse cytochrome c, E148Q mutant enzyme
1200
cytochrome c
-
reconstituted wild-type enzyme
1200
cytochrome c
-
horse cytochrome c, D195Q mutant enzyme
1300
cytochrome c
-
wild-type enzyme
1300
cytochrome c
-
horse cytochrome c, D151N/E152Q mutant enzyme
1400
cytochrome c
-
recombinant D407N mutant enzyme
1500
cytochrome c
-
horse heart cytochrome c
1600
cytochrome c
-
horse cytochrome c, D188N/E189Q mutant enzyme
1700
cytochrome c
-
horse cytochrome c, wild-type enzyme
2000
cytochrome c
-
recombinant enzyme
8
cytochrome c549
-
-
-
1.3
cytochrome c550
-
-
37.4
cytochrome c550
-
Magnetospirillum magnetotacticum cytochrome c550
4
cytochrome c552
-
-
-
9.78
cytochrome c552
-
-
-
252
cytochrome c553
-
-
-
15.3
diaminodurene
-
ascorbate/diaminodurene assay system
1
ferrocytochrome c
-
at 7C, in presence of 56% ethylene glycol
3.93
N,N,N',N'-tetramethyl-p-phenylendiamine
-
ascorbate/N,N,N',N'-tetramethyl-p-phenylendiamine assay system
7.5
N,N,N',N'-tetramethyl-p-phenylendiamine
-
-
60
N,N,N',N'-tetramethyl-p-phenylendiamine
-
ascorbate/N,N,N',N'-tetramethyl-p-phenylendiamine assay system
180
N,N,N',N'-tetramethyl-p-phenylendiamine
-
-
220
N,N,N',N'-tetramethyl-p-phenylendiamine
-
-
24.3
phenazine methosulfate
-
ascorbate/phenazine methosulfate assay system
30
reduced cytochrome c551
-
mutant enzyme E116Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
140
reduced cytochrome c551
-
mutant enzyme D99N, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
199
reduced cytochrome c551
-
mutant enzyme E66Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
200
reduced cytochrome c551
-
mutant enzyme D49N, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
290
reduced cytochrome c551
-
mutant enzyme E68Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
295
reduced cytochrome c551
-
wild type enzyme, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
297
reduced cytochrome c551
-
mutant enzyme E139Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
317
reduced cytochrome c551
-
mutant enzyme E64Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
325
reduced cytochrome c551
-
mutant enzyme E84Q, at 40C, 200 mM KCl, 1 mM MgSO4, 1 mM sodium phosphate buffer, pH 6.8
-
12
ferrocytochrome c
-
at 7C in absence of ethylene glycol
additional information
additional information
-
kcat increases with decreasing pH
-
additional information
additional information
-
above 20 mM phosphate: rapid decrease of kcat with Candida krusei, tuna, Thiobacillus novellus, and horse cytochrome c
-
additional information
additional information
-
highest turnover number at 55 mM ionic strength: D214N, D195N and E148Q, highest turnover number at 45 mM ionic strength: E157Q, comparison of high and low affinity turnover numbers at low ionic strength with Rhodobacter spaeroides and horse cytochrome c of wild-type and various mutants
-
additional information
additional information
-
study of reaction kinetics assuming a fast protonic phase with a proton transfer to H291 and a slow process with a proton transfer to OH-group of binuclear catalytic site. Comparison with kinetics of enzyme from Rhodobacter spaeroides and Paracoccus denitrificans
-
additional information
additional information
-
study of reaction kinetics assuming a fast protonic phase with a proton transfer to H291 and a slow process with a proton transfer to OH-group of binuclear catalytic site. Comparison with kinetics of enzyme from Rhodobacter spaeroides and Bos taurus
-
additional information
additional information
-
study of reaction kinetics assuming a fast protonic phase with a proton transfer to H291 and a slow process with a proton transfer to OH-group of binuclear catalytic site. Comparison with kinetics of enzyme from Paracoccus denitrificans and Bos taurus
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00035
CN-
-
-
0.0005
CN-
-
-
0.0007
CN-
-
horse cytochrome c as electron donor
0.0026
CN-
-
-
0.0045 - 0.005
cyanide
-
-
0.0035
ferricytochrome c
-
at pH 8.0
0.0079
ferricytochrome c
-
at pH 7.0
0.0083
ferricytochrome c
-
at pH 6.0
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0083
4-hydroxynonenal
-
-
0.001
CN-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0025
-
activity in plasma membrane
0.01
-
activity in thylakoid membrane
0.015
-
activity in plasma membrane of heterocysts
0.015
-
activity in thylakoid membrane
0.018
-
-
0.02
-
activity in thylakoid membrane
0.032
B0F2H7
standard male
0.05
-
activity in plasma membrane
0.05
B0F2H7
recently masculinized
0.06
-
activity in plasma membrane
0.12
-
normal muscle
0.217
-
oxidation of horse cytochrome c
0.258
-
in the presence of cardiolipin
0.38
-
activity in thylakoid membrane of heterocysts
0.51
-
sarcoma tissue
4
-
initial membrane fraction, pH 7.0, 25C, N,N,N',N'-tetramethyl-p-phenylene diamine oxidase activity
8.4
-
oxidation of horse ferrocytochrome c
24
-
cytochrome c
50.7
-
oxidation of horse heart cytochrome c
52.5
-
strain MON-1, 19.4fold purified
111
-
purified enzyme, pH 7.0, 25C, N,N,N',N'-tetramethyl-p-phenylene diamine oxidase activity
114
-
oxidation of Candida krusei cytochrome c
147
-
cytochrome c
additional information
-
CuA depleted enzyme shows 15% activity of native and 75% activity of p-(hydroxymercuri)benzoate modified enzyme
additional information
-
spectra of the A, PM, F and O inermediate state of enzyme catalysis by use of a special cuvette to measure optical changes of millisecond freeze-hyperquench powder samples at temperatures below -23C.Catalytic cycle of cytochrome c oxidase at low temperature is similar to that at room temperature
additional information
-
activity of cytochrome-c oxidase from heart is 2-7fold increased when the membrane integrity is disrupted by hypotonic swelling, freeze-thawing, or a detergent
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 6
-
glycylglycine/NaOH buffer
5.5
-
phosphate buffer
5.6
-
electron donor: cytochrome c from Nitrosomonas europaea
5.6
-
oxidation of Candida krusei and Saccharomyces oviformis cytochrome c
5.8
-
oxidation of tuna cytochrome c
5.9
-
oxidation of horse and cow cytochrome c
6 - 6.5
-
-
6
-
electron donor: cytochrome c from Candida krusei
6
-
purified enzyme
6
-
phosphate buffer
6
-
oxidation of Magnetospirillum magnetotacticum cytochrome c550
6.1
-
electron donor: cytochrome c from horse heart and Candida krusei
6.1
-
two-third of optimal activity at pH 5.0 and pH 7.1
6.4
-
electron donor: cytochrome c from Pseudomonas sp. AM1
6.5
-
proton translocation
6.5
-
wild-type, D407A, D407C and D407N mutant enzyme, sharp drop above
7 - 7.5
-
-
7 - 7.6
-
oxidation of {N,N,N,N-tetramethyl-p-phenylenediamine
7
-
stopped-flow measurements
7.4
B0F2H7
activity assay
7.4
-
activity assay
7.5 - 8
-
presence of reducing agents
8
-
oxidation of horse heart cytochrome c
8
-
activity assay
8.3
-
oxidation of ascorbate
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 7.1
-
less than 75% of maximal activity above and below
5.5 - 8
-
proton translocation
additional information
-
redox potential of cytochrome a is pH dependent
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.3
-
calculated value
5.5
-
measured value
9.3
-
calculated
9.6
-
calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
highly stained in AtCOX19-1::GUS plants
Manually annotated by BRENDA team
Q91W29
cortical astrocyte. Differential, cell-type specific expression of enzyme subunit IV isoform 2 in cortical astrocytes and cerebellar neurons. Presence of subunit IV isoform 2 suppresses the sensitivity of enzyme to its allosteric regulator ATP and overrules the regulation by the cellular energy level. Pivotal role of enzyme as an oxygen sensor in brain
Manually annotated by BRENDA team
-
cytochrome-c oxidase activity is abnormal in cerebellar cortex, dentate nucleus, and brainstem regions of Girk2(Wv) (Weaver) mutant mice. Metabolic alterations in cerebellar and vestibular regions are linearly correlated with poor motor coordination
Manually annotated by BRENDA team
Rattus norvegicus Charles-Foster
-
-
-
Manually annotated by BRENDA team
-
primary cardiac cell culture of neonatal rats, increase in enzyme activity by interaction of enzyme subunit IV with protein kinase Cepsilon upon hypoxia
Manually annotated by BRENDA team
Q91W29
cerebellar neurons. Differential, cell-type specific expression of enzyme subunit IV isoform 2 in cortical astrocytes and cerebellar neurons. Presence of subunit IV isoform 2 suppresses the sensitivity of enzyme to its allosteric regulator ATP and overrules the regulation by the cellular energy level. Pivotal role of enzyme as an oxygen sensor in brain
Manually annotated by BRENDA team
-
frontal cortex and posterior cortex
Manually annotated by BRENDA team
-
regular alternation of areas with high and low levels of activity of the respiratory enzyme CO in layers III, IV, and VI of field 17 and in layers IV and VII of field 18 of the cerebral cortex
Manually annotated by BRENDA team
P00415, P00423, P00426, P00428, P00429, P00430, P04038, P07470, P07471, P10175, P13183, P13184
-
Manually annotated by BRENDA team
-
from ammonia-grown cultures
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
thyroid hormone T3 has no effect on COX Vb expression
Manually annotated by BRENDA team
-
downregulation of enzyme activity in the neonatal period by factor 3
Manually annotated by BRENDA team
-
cells proliferate under 80% O2. Under both 20% and 80% O2, mitochondrial reactive oxygen species production is 2fold less in HeLa-80 cells than in wild-type HeLa cells, related to a 2fold higher cytochrome-c oxidase activity. Elevated enzyme activity is associated with a 2fold increase in the regulatory subunit Vb. Treatment with siRNA against subunit Vb lowers its expression, increases mitochondrial generation of reactive oxygen species, decreases enzyme activity by 60-80% and diminishes viability under 80% O2, elevated COX activity in the oxygen-tolerant HeLa-80 cells, associated with a more than 2fold increase in the regulatory subunit COX Vb, whereas expression levels of other subunits are very close to wild-type HeLa-20 cells
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
expression in leaves is only observed when cuts are produced, suggesting an induction by wounding
Manually annotated by BRENDA team
-
lymphoblastoid cells prepared from leucocytes
Manually annotated by BRENDA team
-
thyroid hormone T3 induces concomitant increase in the protein and mRNA expression of nuclear-encoded subunit COX Vb and produces a significant increase in COX III mRNA
Manually annotated by BRENDA team
-
comparison of enzyme activities in liver of arctic and temperate teleosts. Antioxidant enzyme activities may not be enhanced as part of adaptation in arctic fishes, at least not in the liver
Manually annotated by BRENDA team
-
comparison of cytochrome c oxidase activity, instrumental and visual colour, metmyoglobin-reducing activity, and total reducing activity in different types of muscle
Manually annotated by BRENDA team
-
thoracic flight muscle
Manually annotated by BRENDA team
-
psoas major, longissimus lumborum, superficial semimembranosus, deep semimembranosus, and semitendinosus muscle, comparison of cytochrome c oxidase activity, instrumental and visual colour, metmyoglobin-reducing activity, and total reducing activity
Manually annotated by BRENDA team
-
adrenal pheochromocytoma
Manually annotated by BRENDA team
-
comparison of cytochrome c oxidase activity, instrumental and visual colour, metmyoglobin-reducing activity, and total reducing activity in different types of muscle
Manually annotated by BRENDA team
-
highly stained in AtCOX19-1::GUS plants. Activity in roots is already evident at very early stages of development (1-2 days after imbibition), but not in embryos at late stages of embryogenesis and is higher in the root meristem, the vascular cylinder and nascent secondary roots
Manually annotated by BRENDA team
-
superficial and deep semimembranosus, comparison of cytochrome c oxidase activity, instrumental and visual colour, metmyoglobin-reducing activity, and total reducing activity in different types of muscle
Manually annotated by BRENDA team
-
comparison of cytochrome c oxidase activity, instrumental and visual colour, metmyoglobin-reducing activity, and total reducing activity in different types of muscle
Manually annotated by BRENDA team
-
tetracycline-inducible cell line derived from Flp-InTM TRExTM-293 cells (Invitrogen), stably expressing human nitric oxide synthase
Manually annotated by BRENDA team
additional information
-
cortex
Manually annotated by BRENDA team
additional information
-
striatum
Manually annotated by BRENDA team
additional information
P17665
striatum
Manually annotated by BRENDA team
additional information
-
mammalian tissue-specific isoforms
Manually annotated by BRENDA team
additional information
-
1321N cell
Manually annotated by BRENDA team
additional information
-
HeLa-20 cell
Manually annotated by BRENDA team
additional information
-
in C1 cells, C2 cells and C3 cells steady state level of complex I is significantly reduced due to a defective assembly of complex IV. Also present in 4A cells
Manually annotated by BRENDA team
additional information
-
in the central auditory system cytochrome oxidase activity increases in the granular cell layer of dorsal cochlear nucleus, trapezoid body nucleus, intermediate lateral lemniscus, central and external inferior colliculus, and pyramidal cell layer of primary auditory cortex of Relnrl-Orl (reeler) mutant mice, whereas activity decreases in the superficial molecular layer of dorsal cochlear nucleus as well as in the medioventral periolivary nucleus
Manually annotated by BRENDA team
additional information
-
infection of plants with the pathogenic bacterium Pseudomonas syringae pv. tomato induces COX19 gene expression
Manually annotated by BRENDA team
additional information
-
neuronal-glial culture
Manually annotated by BRENDA team
additional information
-
striatum and cortex
Manually annotated by BRENDA team
additional information
Mus musculus C57B6/S129
-
striatum
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
mitochondrion-endoded subunit COXII does not localize exclusively to mitochondria, but is also present in cytosol. COXIV RNA-binding activity, present in the mitochondrial fraction, decreases during development with inverse correlation with accumulation of COXIV precursor in the cytoplasm
Manually annotated by BRENDA team
-
AtCOX19 isoforms are imported into mitochondria in vitro and are attached to the inner membrane facing the intermembrane space
-
Manually annotated by BRENDA team
Mus musculus C57B6/S129
-
-
-
-
Manually annotated by BRENDA team
-
protoplast membrane vesicles
Manually annotated by BRENDA team
-
solubilized with Triton X-100
Manually annotated by BRENDA team
B3SGB4
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB9
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGA9
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGC3
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGA7
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGA8
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB1
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB8
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGC5
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
Q8LWE9
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB0
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
A0ASV2
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB7
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB2
the near N-terminus ca. 2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGC2
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
Q94QP4
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB5
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGC0
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGB6
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGC4
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
B3SGC1
the near N-terminus ca.2/3 of the MCOX2e region contains an interspecifically variable number of predicted transmembrane helices
Manually annotated by BRENDA team
Pseudomonas putida KT2240
-
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa IFO
-
solubilized with Triton X-100
-
Manually annotated by BRENDA team
Geobacillus thermodenitrificans K1041
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
possible arrangement of subunits in membrane
Manually annotated by BRENDA team
synthetic construct
-
-
Manually annotated by BRENDA team
-
mitochondrion-endoded subunit COXII does not localize exclusively to mitochondria, but is also present in cytosol. COXIV RNA-binding activity, present in the mitochondrial fraction, decreases during development with inverse correlation with accumulation of COXIV precursor in the cytoplasm
Manually annotated by BRENDA team
Saccharomyces cerevisiae BY4742
-
intermembrane space
-
Manually annotated by BRENDA team
Mus musculus C57B6/S129, Paracoccus denitrificans AO1, Rattus norvegicus Charles-Foster
-
-
-
Manually annotated by BRENDA team
additional information
-
cytochrome oxidase unilamellar vesicles (COV). Purified COV contains approximately 1 COX molecule per liposome. Purified COV exhibits similar physical properties as unpurified COV
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Bradyrhizobium diazoefficiens (strain JCM 10833 / IAM 13628 / NBRC 14792 / USDA 110)
Rhodobacter sphaeroides (strain ATCC 17023 / 2.4.1 / NCIB 8253 / DSM 158)
Rhodobacter sphaeroides (strain ATCC 17023 / 2.4.1 / NCIB 8253 / DSM 158)
Rhodobacter sphaeroides (strain ATCC 17023 / 2.4.1 / NCIB 8253 / DSM 158)
Rhodobacter sphaeroides (strain ATCC 17023 / 2.4.1 / NCIB 8253 / DSM 158)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5444
P17665
Cox7c, mass spectrometry
694263
18000
P17665
Cox4, immunoblot analysis
694263
35000
P17665
Cox1, immunoblot analysis
694263
56400
-
sequence analysis
692026
67000
-
calculation from heme content
396027
71000
-
calculated
664918
79000
-
SDS-PAGE, no mercaptoethanol
396071
83000
-
calculation from heme content
396069
86000
-
sedimentation analysis
396003
92000
-
SDS-PAGE, no mercaptoethanol
396048
114000
-
analytical ultracentrifugation
396136
115000
-
sedimentation analysis
395996
115000
-
-
396003
116000
-
gel filtration
396048
140000 - 158000
-
sedimentation equilibrium analysis, monomeric form
396039
140000 - 158000
-
-
396083
140000 - 158000
-
calculation from heme content
396083
158000
-
sedimentation equilibrium, monomeric enzyme complex
396039
162000
-
calculation from heme content
396090
170000
-
nondenaturing PAGE
659898
180000 - 280000
-
minimal molecular weight, calculated from subunit composition, heme content
396005, 396007
190000 - 225000
-
sucrose density gradient centrifugation
396093
190000
-
gel filtration
396136
200000
-
heart, monomeric enzyme, deoxycholate solubilized, hydrodynamic measurements
396050
200000
-
gel filtration
396129
204000
-
amino acid sequence of 12 subunits + 6000 Da for subunit VIIb
396065
210000
-
vertebrate, theoretical value of monomer composed of 12-13 different subunits
395999
226000
-
estimated from sucrose density gradient centrifugation and gel filtration
396094
250000
-
gel filtration in the presence of N-lauryl sarcosinate
396077
290000 - 315000
-
gel filtration, value depending on ionic strength
396053
290000 - 315000
-
enzyme associated with detergents
396059
326000
-
dimeric enzyme complex, sedimentation equilibrium centrifugation
396039
350000
-
dimeric form, Triton X-100 solubilized, hydrodynamic measurements
396050
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 30500 + x * 25500 + x * 12200 + x * 9500, SDS-PAGE
?
-
x * 55000 + x * 29500 + x * 19000 + x * 13000 + x * 11000 + x * 5700, homolog to eukaryotic subunit III is lost during purification, SDS-PAGE
?
-
x * 32000 + x * 23000, SDS-PAGE
?
-
x * 45000 + x * 37000 + x * 35000, SDS-PAGE
?
-
x * 47000 + x * 31000 + x * 19000, SDS-PAGE
?
-
x * 39000 + x * 28000, SDS-PAGE
?
-
x * 50000 + x * 30000, SDS-PAGE
?
-
I, II, III, IV, V, x * 39000 + x * 33500 + x * 26000 + x * 20000 + x * 5700, probably 2 more small subunits, SDS-PAGE
?
-
x * 12233, MALDI-TOF, x * 12236, calculated
?
-
x * 12723, MALDI-TOF, x * 12724, calculated
?
Pseudomonas sp. AM1
-
x * 50000 + x * 30000, SDS-PAGE
-
dimer
-
1 * 55000 + 1 * 32000, SDS-PAGE
dimer
-
1 * 58000 + 1 * 26000, 58000 Da band may be composed of 2 subunits of the cb-type oxidase, the 26000 Da subunit may be a heme c bearing diheme or mono-heme of the enzyme, SDS-PAGE
dimer
-
1 * 55000 + 1 * 32000, SDS-PAGE, immunoblotting
dimer
-
1 * 39000 + 1 * 28000, SDS-PAGE
dimer
-
2 subunits, analogous to subunits I and II of eukaryotes
dimer
-
1 * 22000-26000 + 1 * 14000-17000, SDS-PAGE, immunoblotting
dimer
-
1 * 48000-49000 + 1 * 36000, SDS-PAGE, immunoblotting
dimer
-
1 * 71600 + 1 * 34300, densitometric scan
dimer
-
1 * 46000-55000 + 1 * 29000-32000, SDS-PAGE, immunoblotting
dimer
-
1 * 50000 + 1 * 33000, SDS-PAGE
dimer
-
2 * 43000, SDS-PAGE, 0.5% 2-mercaptoethanol
dimer
-
1 * 49000-50000 + 1 * 42000-43000, SDS-PAGE, immunoblotting
dimer
-
1 * 54000 + 1 * 32000, SDS-PAGE
dimer
-
1 * 55000 or 71000 + 1 * 33000, SDS-PAGE
dimer
-
1 * 51000 + 1 * 31000, SDS-PAGE, Ferguson plot
dimer
-
1 * 30000 + 1 * 50000, SDS-PAGE
dimer
-
1 * 45000 + 1 * 28000, SDS-PAGE
dimer
-
1 * 40000 + 1 * 27000, SDS-PAGE
dimer
-
1 * 23000 + 1 * 32000, SDS-PAGE
dimer
-
1 * 71000 + 1 * 34000, subunit I shows anomalous behaviour on SDS-PAGE, Ferguson plot
dimer
-
1 * 55000 + 1 * 33000, SDS-PAGE
dimer
-
CuCox19 and apoCox19, sedimentation equilibrium
dimer
Saccharomyces cerevisiae BY4742
-
CuCox19 and apoCox19, sedimentation equilibrium
-
dimer
Pseudomonas sp. AM1
-
1 * 30000 + 1 * 50000, SDS-PAGE
-
heterotrimer
-
1 * 60371 + 1 * 17074 + 1 * 5976, calculated from amino acid sequence
heterotrimer
Geobacillus thermodenitrificans K1041
-
1 * 60371 + 1 * 17074 + 1 * 5976, calculated from amino acid sequence
-
oligomer
-
-
oligomer
-
-
oligomer
-
-
oligomer
-
-
oligomer
-
I, II, III, IV, Va, Vb, VIIa, VIIc, VIII, 1 * 56000 + 1 * 26678 + 1 * 30340 + 1 * 14858 + 1 * 12627 + 1 * 14570 + 1 * 6603 + 1 * 5364 + 1 * 6303, amino acid sequences
oligomer
-
I, II, III, IV, V, VI, VII, 1 * 34000 + 1 * 23000 + 1* 20000 + 1 * 17500 + 1 * 13000 + 1 * 10000 + 1 * 6000, SDS-PAGE
oligomer
-
I, II, III, IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, VIIc, VIII, 1 * 56993 + 1 * 26049 + 1 * 29918 + 1 * 17153 + 1 * 12436 + 1 * 10670 + 1 * 9419 + 1 * 10068 + 1 * 8480 + 1 * 5441 + 1 * 6244 + 1 * 6350 + 1 * 4962, heart, 13 subunits, nomenclature system of subunits according to Kadenbach et. al, BRENDA reference 396096 (PubMed-ID 6303162), and literature cited therein, other nomenclature systems, amino acid sequences
oligomer
-
I, II, III, IV, V, VI, VII, 1 * 40000 + 1 * 29000 + 1 * 21000 + 1 * 18000 + 1 * 14000 + 1 * 12000 + 1 * 9000, proposed subunit composition, stoichiometry
oligomer
-
I, II, III, IV, V, VI, VII, 1 * 35100 + 1 * 23100 + 1* 21300 + 1 * 17900 + 1 * 11600 + 1 * 8750 + 1 * 4600, possibly multiple subunits at position VII, SDS-PAGE
oligomer
-
I, II, III, IV, V, VI, VII, 1 * 43600 + 1 * 20100 + 1* 18000 + 1 * 13700 + 1 * 8800 + 1 * 5600 + 1 * 3700, SDS-PAGE
oligomer
-
cytochrome c oxidase is composed by 13 subunits
oligomer
-
mitochondrial COX consists of up to 13 subunits
tetramer
-
1 * 29000, 1 * 21000, 1 * 11500, 1 * 9500, SDS-PAGE
tetramer
Pseudomonas aeruginosa IFO
-
1 * 29000, 1 * 21000, 1 * 11500, 1 * 9500, SDS-PAGE
-
trimer
-
1 * 58360 + 1 * 34840 + 1 * 23470, MALDI-TOF mass spectrometry, 1 * 41000 + 1 * 35000 + 1 * 26000, SDS-PAGE
trimer
-
1 * 56000 + 1 * 40000 + 1 * 14000, SDS-PAGE
trimer
-
1 * 52000 + 1 * 37000 + 1 * 29000, SDS-PAGE
trimer
-
1 * 43000 + 1 * 34000 + 1 * 28000, SDS-PAGE, 5% 2-mercaptoethanol
trimer
-
1 * 45000 + 1 * 28000 + 1 * 23000, SDS-PAGE
trimer
-
1 * 54950 + 1 * 27850 + 1 * 22400, SDS-PAGE
trimer
-
1 * 35000 + 1 * 37000 + 1 * 45000, SDS-PAGE
trimer
-
1 * 56000 + 1 * 38000 + 1 * 22000, SDS-PAGE, Ferguson plot
trimer
-
1 * 57000 + 1 * 37000 + 1 * 21000, SDS-PAGE
trimer
-
1 * 57000 + 1 * 37000 + 1 * 22000, SDS-PAGE
trimer
-
1 * 57000 + 1 * 37000 + 1 * 22000, SDS-PAGE
trimer
-
1 * 38000, 1 * 57000, 1 * 82000
trimer
Bacillus subtilis W23
-
1 * 57000 + 1 * 37000 + 1 * 21000, SDS-PAGE
-
monomer
-
1 * 65000, b heme
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
liver enzyme, 1/1 stoichiometry of subunits
additional information
-
subunits I, II, and III detected by immunoblotting, a mitochondria-like subunit IV that may confer allosteric properties to the enzyme is also suggested
additional information
-
approx. 10 different subunits after 2D gel electrophoresis
additional information
-
X-ray data: subunits form a dimeric quarternary structure that may also exist under physiological conditiones
additional information
-
proposed folding patterns of subunits
additional information
-
proposed folding patterns of subunits
additional information
-
subunit arrangement
additional information
-
brain enzyme from swayback-diseased animals is deficient of subunits II, III and IV
additional information
-
mitochondrial cytochrome oxidase c tends to be a dimer
additional information
-
13 different subunits in 1/1 stoichoimetric amounts
additional information
-
differences in small subunit composition depending on source of enzyme
additional information
-
definitions of functional unit
additional information
-
enzyme complex contains eleven rather than twelve subunits
additional information
-
overview nomenclature systems
additional information
-
subunit analysis by reverse phase HPLC
additional information
-
fetal enzyme complex differs from adult heart complex by migration differences of subunits VIa and VIII
additional information
-
sequence alignment with bovine heart
additional information
-
subunit structure, arrangement of subunits in enzyme complex
additional information
-
amino acid sequence of subunit IV
additional information
-
enzyme complex of 7 polypeptide components
additional information
-
separation of subunits
additional information
-
role of subunit III in the mechanism of the proton pump
additional information
-
enzyme complex of 13 polypeptide components
additional information
-
sequence alignments of subunits I, II and III of various eukaryotic and prokaryotic organisms
additional information
-
enzyme complex of 9 polypeptide components
additional information
-
it is suggested that the mitochondrial encoded subunits I, II and III are the catalytic core of the enzyme
additional information
-
composed of more than 10 different protein subunits
additional information
-
hydrophilic domains of COX subunit III are conformationally linked to the electron transfer function of the enzyme in subunit I and II. Subunit III may serve as a regulatory subunit for COX electron transfer and proton pumping activities
additional information
-
the enzyme is built up with both nucleus and mitochondrion-encoded subunits
additional information
-
copper-binding protein SCO1 is involved in the assembly of mitochondrial cytochrome-c oxidase. It functions not as a cytochrome-c oxidase copper chaperone, but rather as a mitochondrial redox signaling molecule
additional information
-
enzyme complex lacking subunit III exhibits a shorter catalytic life span and absence of subunit III dramatically slows proton uptake to the active site via the D proton pathway. Arachidonic acid stimulates proton uptake by the D pathway and retards suicide inactivation. Average catalytic life span of detergent-solubilized complex lacking subunit III decreases dramatically with pH. Maintenance of rapid proton transfer through the D pathway and the backflow/exit pathway is one mechanism by which subunit III normally functions to prevent uicide inactivation of cytochrome c oxidase
additional information
-
enzyme interacts with hepatitis B virus X protein
additional information
-
upon exposure of cells to hypoxia, enzyme subunit IV interacts with protein kinase Cepsilon resulting in increase in cytochrome c oxidase activity
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospholipoprotein
-
-
phospholipoprotein
-
phospholipid content close to 20%
phospholipoprotein
-
10-24% phospholipid
phosphoprotein
-
cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity
phospholipoprotein
-
-
phospholipoprotein
-
-
phospholipoprotein
-
0.037 mg/mg enzyme
phospholipoprotein
-
phospholipid content close to 20%
phospholipoprotein
-
2-3.8% phospholipid
phospholipoprotein
-
approx. 0.012 mmol/mg protein
phospholipoprotein
-
approx. 0.09-0.15 mmol/mg protein
additional information
-
comparison of two oxidized states of enzyme, the state as isolated in the fast form, and the form obtained immediately after oxidation of fully reduced cytochrome-c oxidase with O2. No observable differences are found between these two states
phospholipoprotein
-
-
additional information
-
thyroid hormone T3 regulates the expression of COX subunits by both transcriptional and posttranslational mechanism
lipoprotein
-
subunit III binds two lipids within a deep cleft. Altering the lipid binding sites mimics a major loss of subunit III, even though subunit III is completely retained, in that suicide inactivation becomes much more probable
additional information
Q53111
covalent link between Y311 and the copper-ligating histidine residue
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
concentration of the purified enzyme by Amicon ultrafiltration in 0.3-1 mM or 10 mM sodium phosphate buffer, dimeric in crystal lattice
-
enzyme from heart can be crystallized in hexagonal, tetragonal and orthorhombic forms
-
in complex with CO, NO, and CN-
-
two-dimensional crystals by insertion of the enzyme into preformed lipid vesicles
-
X-ray structure of heart cytochrome c oxidase in the fully oxidized state
-
-
P98002 and P08306
sitting drop vapour diffusion, 200 mM Zn acetate, 100 mM Na acetate, pH 4.5, 19-22% polyethylene glycol 1000, 10 mg/ml enzyme concentration, hexagonal red crystals appear after 3 d at 20C
-
by sitting drop vapor diffusion method
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
irreversible denaturation below, protection by incorporation into proteoliposomes
396013
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
12 h: inactivation
391156
4
-
instable
396073
50
-
loss of activity above within a few min
396036
60
-
10 min, 100% activity
396086
63
-
10 min, 100% activity
396087
70
-
10 min, 50% activity
396087
80
-
10 min, 76% activity
396086
81
-
inactivation, no protection by phospholipids
396029
additional information
-
cold labile
396036
additional information
-
not cold labile
396036
additional information
-
thermal denaturation in lipid phase consisting of 4 sequential melting steps, beginning with denaturation of subunit III
396107
additional information
-
maltoside: increase in thermal stability
396108
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
LiCl, 5 M, stable
-
urea, 1 M, stable
-
ultrafiltration causes inactivation
-
depletion of lipids causes inactivation
-
inactivation by centrifugation of pure complex
-
glycerol: no stabilization during storage
-
inactivation by repeated freezing/thawing
-
unstable to repeated freezing and thawing
-
unstable during purification
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimethyl sulfoxide
-
no inactivation
dimethylformamide
-
no inactivation
Ethanol
-
60%, no inactivation
Ethanol
-
40% v/v, stable
Ethylene glycol
-
60%, no inactivation
Methanol
-
60%, no inactivation
propanediol
-
no inactivation
propanol
-
60%, no inactivation
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-60C, 100 mM phosphate buffer, pH 7.4, 1% Tween 80
-
-70C, concentrated solution
-
-80C, 20 mM Tris-Cl buffer, pH 7.4, 250 mM sucrose, 2 mM EDTA
-
4C, 0.2 M phosphate buffer, 2% cholate, decrease of solubility during long term storage
-
-80C, 5 mM Tris-cacodylate buffer, pH 7.6
-
-80C, no severe loss of activity
-
-70 stable
-
4C, solubilized enzyme, several h, liquid N2, several months
-
-80C, several months
-
0C, up to 7 days
-
liquid N2, 10 mM Tris-HCl buffer, pH 8.0, 0.5% Tween 20
-
-20C, 10 mM Tris-HCl buffer, pH 8.0, 0.5% Tween 20, several months, stable
-
liquid N2, 10 mM Tris-HCl buffer, pH 8.0, 0.5% Tween 20
-
-70C, 10 mM Tris-HCl buffer, pH 7.3, 0.1% cholate
-
0C, 100 mM, potassium phosphate, pH 7.4, 0.5% Tween 20, 6 d, 40-50% loss of activity
-
-70C, 50% glycerol or propylene glycol
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partially purified
-
strain MON-1 purified 19.4fold by gel filtration
-
partial, Mono Q
-
Triton X-100, DEAE-Sepharose, hydroxyapatite, Sephadex G-200
-
literature overview
-
Triton X-100, DEAE-cellulose, DEAE-toyopearl, hydroxyapatite, ammonium sulfate
-
hydroxyapatite S-sepharose
-
method 1: cytochrome c affinity chromatography, ion-exchange, method 2: ammonium sulfate, anion exchange, gel filtration
-
affinity chromatography on horse heart ctochrome c
-
by gel filtration
-
by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification; by small-scale immunopurification
P00415, P00423, P00426, P00428, P00429, P00430, P04038, P07470, P07471, P10175, P13183, P13184
; sodium cholate, ammonium sulfate, dispersion in 0.5% Tween 80
-
hydrophobic chromatography, affinity chromatography on horse cytochrome c
-
DEAE-cellulose, Sephacryl S-300
-
DEAE-Toyopearl column chromatography and hydroxyapatite column chromatography
-
Cu-deficient enzyme
-
Triton X-100, Q-Sepharose, chelating Sepharose, gel filtration
-
DEAE-cellulose, ammonium sulfate
-
sucrose monocaprate, DEAE-Toyopearl
-
method for subunit III depleted enzyme
-
gel filtration, ammonium sulfate, ion-exchange, affinity chromatography on yeast cytochrome c-Sepharose
-
poly-L-lysine agarose, TMAE-fractogel, hydroxyapatite
-
mitochondria are isolated
-
mitochondria are prepared
-
mitochondrial membranes are prepared
-
partially purified by gel filtration
P17665
; affinity chromatography on horse heart cytochrome c
-
Triton X-100, DEAE-cellulose, Sephadex G-150
-
normal and CuA-deficient forms of the enzyme
-
Triton X-100, DEAE-cellulose, Sephacryl S-300
-
literature overview
-
native four-subunit CcO aa3
-
one-subunit enzyme, fully active
-
wild-type and Y280H mutant enzyme
-
wild-type of soluble CuA domain and its mutants W121Y, DELTAW121 and W121L, expressed in Escherichia coli
-
inactivation during purification
-
DEAE-cellulose, Sephacryl S-200
-
DEAE-Toyopearl, Cu2+-immobilized affinity chromatography
-
by differential solubilization
-
by gel filtration
-
Triton X-114, DEAE-sephacel, ammonium sulfate
-
affinity chromatography on yeast cytochrome c
-
on Ni-NTA column
-
polyhistidine-labeled protein purified on a Ni-NTA column
-
recombinant enzyme, Ni2+-nitrilotriacetic acid, DEAE-5PW
-
recombinant wild-type, D407A, D407C and D407N mutant enzyme, Ni2+-nitrilotriacetic acid affinity chromatography
-
by size exclusion chromatography
-
hydroxyapatite, Sepharose CL-6B
-
sucrose gradient ultracentrifugation
-
sodium cholate, ammonium sulfate, dispersion in 0.5% Tween 80
-
literature overview
-
Triton X-100, ammonium sulfate, DEAE-cellulose, Sephadex G-150
-
carboxymethyl cellulose, affinity chromatography on thiopropyl-Sepharose, subunit VIIc
-
tissue-specific isozymes
-
literature overview
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNAs from both COX19-1 splice variants cloned in the sense and antisense orientations in plasmid pYPGE15, containing a constitutive phosphoglycerate kinase gene promoter and a CYC1 terminator. Expressed in a yeast cox19 null mutant
-
cDNA of subunits IV, Vb, VIa, VIb, VIc, VIIb, VIIc, and VIII
-
wild-type cytochrome aa3 gene on plasmid
-
expressed in cloned embryos which derive from Danio rerio embryonic nuclei and Gobiocypris rarus enucleated eggs
-
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
-
cDNA of subunits IV, V, VI and possibly VII
-
wild-type of soluble CuA domain and its mutants W121Y, DELTAW121 and W121L are expressed in Escherichia coli BL21
-
Production of cytochrome c oxidase deficient strains and ANR deficient strain.
Q88RM6
cDNA of subunits IV, Va, VIa, VIc
-
cDNA of subunits VIc and VIII
-
for the preparation of transcripts the plasmid GC-BS-COXIV-3'-UTR is used
-
overexpression in Rhodobacter sphaeroides
-
overexpression of wild-type, D407A, D407C and D407N mutant enzyme in Rhodobacter sphaeroides
-
overexpression of wild-type, E148Q, D195N, E157Q, D214N, D188Q/E189N, D151Q/E152N, W143F, W143A and Y144A/W145A in Rhodobacter sphaeroides
-
overexpressed in DELTAshy1 strain
-
recombinant Cox19 expressed in Escherichia coli BL21 (pLysS) as a fusion protein with an 8-residue C-terminal Strep-tag II extension
-
the soluble CuA domain of subunit II of cytochrome c oxidase is cloned for expression in Escherichia coli cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme activity declines progressively with age between 10 and 47 days by 33%
-
Leigh syndrome most frequent trigger is deficiency of cytochrome c oxidase caused by mutations in the SURF1 gene
-
mutated human superoxide dismutase, SOD1, decreases the Cytox activity, but not the protein content of the Cytox subunit II
-
exposure of mouse Hepa1-6 cells to 10-30 microM pyrroloquinoline quinone for 24-48 h results in increased cytochrome c oxidase activity
-
expression of gelsolin in APP/Ps1 mice increases mitochondrial complex IV activity
-
purified actin and Hsp90 maintain RNA-binding ability and specifity, inhibiting the COXIV messenger translation
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D49N
-
the mutant shows increased Km and reduced kcat values compared to the wild type enzyme
D99N
-
the mutant shows strongly increased Km and reduced kcat values compared to the wild type enzyme
E116Q
-
the mutant shows slightly reduced Km and strongly reduced kcat values compared to the wild type enzyme
E139Q
-
the mutant shows increased Km and slightly increased kcat values compared to the wild type enzyme
E64Q
-
the mutant shows increased Km and kcat values compared to the wild type enzyme
E66Q
-
the mutant shows increased Km and kcat values compared to the wild type enzyme
E68Q
-
the mutant shows increased Km and reduced kcat values compared to the wild type enzyme
E84Q
-
the mutant shows increased Km and reduced kcat values compared to the wild type enzyme
E116Q
Geobacillus thermodenitrificans K1041
-
the mutant shows slightly reduced Km and strongly reduced kcat values compared to the wild type enzyme
-
E139Q
Geobacillus thermodenitrificans K1041
-
the mutant shows increased Km and slightly increased kcat values compared to the wild type enzyme
-
E64Q
Geobacillus thermodenitrificans K1041
-
the mutant shows increased Km and kcat values compared to the wild type enzyme
-
E66Q
Geobacillus thermodenitrificans K1041
-
the mutant shows increased Km and kcat values compared to the wild type enzyme
-
E84Q
Geobacillus thermodenitrificans K1041
-
the mutant shows increased Km and reduced kcat values compared to the wild type enzyme
-
A122T
P00395
recurrent missense mutation in mitochondrially encoded cytochrome oxidase I found in a variety of human cancer cells
D124N
-
subunit I mutant. Reduction of heme a3-CuB is severely impaired, about 0.8 H+ is promptly bound synchronously with the reduction of heme a, followed by a much slower protonation associated with the retarded reduction of the heme a3-CuB site
I347Q
-
16% activity compared to the wild type enzyme
K354M
-
subunit I mutant. Reduction of heme a3 is totally impaired, overall H+ uptake within 10 s is significantly smaller than in the wild-type
R473Q
-
16% activity compared to the wild type enzyme
R474Q
-
41% activity compared to the wild type enzyme
R54M
-
low turnover number, changes in spectral properties of heme a, lowered midpoint redox potential, electron transfer from CuA to heme a is impaired
T50A
-
90% activity compared to the wild type enzyme
T50N
-
50% activity compared to the wild type enzyme
V279I
-
50% activity compared to the wild type enzyme
Y280H
-
catalytic site retains its active configuration that allows O2 binding to heme a3
Y339F
-
64% activity compared to the wild type enzyme
Y406F
-
40% activity compared to the wild type enzyme
DELTAW121
-
mutant of the soluble CuA domain, both the coordination structure of the CuA center and the secondary structure of the protein are changed significantly, the electron transfer activity with cytochrome c is inhibited severely
W121L
-
mutant of the soluble CuA domain, both the coordination structure of the CuA center and the secondary structure of the protein are changed significantly, the electron transfer activity with cytochrome c is inhibited severely
W121Y
-
mutant of the soluble CuA domain, stability decreases compared with the wild-type enzyme. The mutant keeps the same secondary structure as the wild-type protein, but can only transfer electrons with cytochrome c at a rate of one-seventh-fold
A205T
-
mutation in subunit III associated with mitochondrial disease, no change in subunit composition of the complex
D132A
-
mutation of initial proton acceptor of the D pathway. Average catalytic life span of D132A complex lacking subunit III is 2-fold to 50-fold less than that of wild-type complex lacking subunit III, depending upon pH, and the catalytic life span of D132A complex lacking subunit III is independent of external pH from pH 6.2 to pH 7.4
D132A/R481K
-
catalytic life span of D132A/R481K holo complex is 10fold shorter than that of wild-type holo complex
D132N
-
proton donor E286 is present, but its reprotonation from the N side of the membrane is blocked
D151Q/E152N
-
similar steady-state kinetic as wild-type
D188Q/E189N
-
similar steady-state kinetic as wild-type
D195N
-
decrease in activity, increase in Km
D214N
-
decrease in activity, increase in Km
D407A
-
similar properties as wild type, suggesting that D407 does not play a role in proton translocating
D407C
-
similar properties as wild type, suggesting that D407 does not play a role in proton translocating
D407N
-
similar properties as wild type, suggesting that D407 does not play a role in proton translocating
D485A
-
mutant enzyme is active, binds to Ca2+ reversibly, and exhibits the red shift in the heme a absorption spectrum upon Ca2+ binding for both reduced and oxidized states of heme a. Sodium ions reverse the Ca2+-induced red shift of heme a and dramatically decrease the rate of Ca2+ binding to the mutant enzyme. With the mutant enzyme, 1 Ca2+ competes with 1 Na+ for the binding site
E101A
-
mutation in subunit II strongly reduces oxidase activity to 8%
E101A
-
exhibits low activity and eliminates metal binding at this site. Significant activity is restored by adding lipophilic carboxylic compounds (arachidonic acid and cholic acid), but not by their non-carboxylic analogues
E101A/H96A
-
exhibits low activity and eliminates metal binding at this site. Significant activity is restored by adding lipophilic carboxylic compounds (arachidonic acid and cholic acid), but not by their non-carboxylic analogues. Activity is still inhibited by zinc, but this remaining inhibition is nearly eliminated by removal of subunit III
E101C
-
mutation in subunit II strongly reduces oxidase activity to 8%
E101D
-
mutation in subunit II strongly reduces oxidase activity to 16%
E101H
-
mutation in subunit II strongly reduces oxidase activity to 19%
E101I
-
mutation in subunit II strongly reduces oxidase activity to 8%
E101N
-
mutation in subunit II strongly reduces oxidase activity to 17%
E101Q
-
mutation in subunit II strongly reduces oxidase activity to 14%
E148Q
-
decrease in activity, increase in Km
E157Q
-
decrease in activity, increase in Km
E286A/I112E
-
about 2% of wild-type activity in the holo complex, mutant complex lacking subunit III exhibits a very short average catalytic life span of approximately 100 catalytic cycles
E286D
-
mutation in D pathway. E286D complex lacking subunit III exhibits a 75% decrease in its O2 reduction activity, compared to wild-type complex lacking subunit III. Catalytic life span of detergent-solubilized E286D complex lacking subunit III is half that of wild-type complex lacking subunit III or about the same as D132A complex lacking subunit III
E286Q
-
absence of both protonic phases in enzyme kinetics. Mutant is not able to generate the ferryl-oxo form under the experimental conditions applied
E54A/D485A
-
inactive mutant enzyme does not assemble normally
E54L
-
inactive mutant enzyme does not assemble normally
E54L/D485A/Q61L
-
inactive mutant enzyme does not assemble normally
E54L/Q61L
-
inactive mutant enzyme does not assemble normally
F86A
-
mutation in subunit III, results in an enzyme complex that contains only about 50-70% of subunit III compared with wild-type
F93A
-
mutation in subunit III, results in an enzyme complex that contains only about 40-60% of subunit III compared with wild-type
G78S
-
mutation in subunit III associated with mitochondrial disease, no change in subunit composition of the complex
H260N
-
mutant of CuA center, the rate constant for the intramolecular electron transfer from heme c to CuA is decreased from 40000 per s for the wild-type enzyme to 11000 for the mutant enzyme, the rate constant for intracomplex electron transfer from CuA to heme a is decreased from 90000 per s for wild-type enzyme to 45 per s for the mutant. The rate constant for the reverse reaction, heme A to CuA, is 180 per s for the mutant enzyme, compared to 17000 for the wild-type enzyme. The redox potential of CuA is increased by 90 mV relative to hemeA
H300A
-
mutation in subunit I increases oxidase activity to 111%
K362M
-
enzyme with mutation in subunit I is inactive
L100AV
-
mutation in subunit II increases oxidase turnover to 45%
L145A/L196A/L203A
-
mutation in subunit I at sites in contact with the fatty acid tails of subunit III, no effect on the content of subunit III in the complex
M263L
-
mutant of CuA center, the rate constant for the intramolecular electron transfer from heme c to CuA is decreased from 40000 per s for the wild-type enzyme to 16000 for the mutant enzyme, the rate constant for intracomplex electron transfer from CuA to heme a is decreased from 90000 per s for wild-type enzyme to 4000 per s for the mutant. The rate constant for the reverse reaction, hemeA to CuA, is 66000 per s for the mutant enzyme, compared to 17000 for the wild-type enzyme. The redox potential of CuA is increased by 120 mV relative to hemeA
N139D
-
turnover rate is increased by a factor of 2-3, mutant does not pump protons
Q61A
-
mutant enzyme is active and retains tighly bound Ca2+
Q61L
-
mutant enzyme is active and retains tighly bound Ca2+
R137A
-
mutation in subunit I, results in an enzyme complex that contains only about 5-25% of subunit III compared with wild-type
R226A
-
mutation in subunit III, results in an enzyme complex that contains only about 90% of subunit III compared with wild-type
R481K
-
mutant retains substantial activity and is able to pump protons, but at somewhat reduced rates and stoichiometry
R482A
-
mutant retains substantial activity and is able to pump protons, but at somewhat reduced rates and stoichiometry
R482K
-
mutant retains substantial activity and is able to pump protons, but at somewhat reduced rates and stoichiometry
R482P
-
mutant enzyme is perturbed in its structure and is altered in the redox potential difference between heme a and CuA: 18 mV for R482P compared to +46 mV for the wild-type (hemea - CuA). The electron tranport rate between CuA and heme A is also altered from 93000 per s in the wild-type to 50 per s in the oxidized R482P mutant
R482Q
-
mutant retains substantial activity and is able to pump protons, but at somewhat reduced rates and stoichiometry
S299A
-
mutation in subunit I reduces oxidase activity to 45%
S89A
-
mutation in subunit III, loss of side-chain interaction between S89 and F86 does not affect assembly of the enzyme complex
T359A
-
mutation of K pathway. Steady-state activity of T359A complex lacking subunit III is 20% that of wild-type complex lacking subunit III, and life span is similar to wild-type
W104V
-
mutation in subunit II reduces oxidase activity to 45%
W105A
-
mutation in subunit II reduces oxidase activity to 50%
W143A
-
similar copper/Fe ratios as wild-type
W143F
-
similar copper/Fe ratios as wild-type
W58A
-
mutation in subunit III, results in an enzyme complex that contains only about 50-70% of subunit III compared with wild-type
W59A
-
mutation in subunit III, results in an enzyme complex that contains only about 50-70% of subunit III compared with wild-type
W59A/F86A
-
mutation in subunit III, results in an enzyme complex that contains only about 60-80% of subunit III compared with wild-type
Y311F
Q53111
no enzymic activity, protein complex is correctly assembled
C30A
-
is growth-compromised on glycerol/lactate. Is compromised in Cu(I) binding
C30A/C62A
-
is growth-compromised. Is more severely compromised than the single C30A mutant. Fails to accumulate in mitochondria. Is compromised in Cu(I) binding
C40A/C52A
-
is functional
H26A
-
is able to propagate on glycerol/lactate medium
R63T
-
is nonfunctional even when expressed as an IM-tethered Cox19 fusion
C30A
Saccharomyces cerevisiae BY4742
-
is growth-compromised on glycerol/lactate. Is compromised in Cu(I) binding
-
C30A/C62A
Saccharomyces cerevisiae BY4742
-
is growth-compromised. Is more severely compromised than the single C30A mutant. Fails to accumulate in mitochondria. Is compromised in Cu(I) binding
-
C40A/C52A
Saccharomyces cerevisiae BY4742
-
is functional
-
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
additional information
-
an assembled complex IV is required to maintain the stability of complex I in a mouse cell line with suppressed expression of subunit 4 of complex IV
M55A
-
mutation in subunit III, results in an enzyme complex that contains only about 30-50% of subunit III compared with wild-type
additional information
-
mutant lacking Surf1p involved in assembly of cytochrome-c oxidase shows three subpopulations of enzyme with structurally distinct heme a3-CuB active sites, 50% of enzyme lacks heme a3, 10-15% contains heme a3 but lacks CuB. CuA assembly is unaffected
H26A/C30A
-
is growth-compromised. Fails to accumulate in mitochondria. Is compromised in Cu(I) binding
additional information
-
CcO activity in cox19DLETA cells is less than 10% of wild-type levels
H26A
Saccharomyces cerevisiae BY4742
-
is able to propagate on glycerol/lactate medium
-
additional information
Saccharomyces cerevisiae BY4742
-
CcO activity in cox19DLETA cells is less than 10% of wild-type levels
-
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme reconstituted into lipid vesicles generates membrane potential
-
reconstitution
-
proton pumping activity of cytochrome c oxidase reconstituted in phospholipid vesicles
-
reconstitution into dimyristoylphosphatidylcholine vesicles
-
reconstitution into phospholipid vesicles; reconstitution into phospholipid vesicles in the presence of hydrophobic poly(vinyl alkanoate) polymers
-
reconstitution methods
-
reconstitution of proton pumping activity
-
overview of methods for reconstitution
-
reconstitution into phospholipid vesicles
-
reconstitution into phospholipid vesicles
-
reconstitution into phospholipid vesicles, enzyme acts as proton pump
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
cytochrome c oxidase modified electrodes can be used to distinguish amino acid sequence variations in proteins such as cytochrome c. This has potential relevance as a diagnostic for disease states, characterization of electron transfer reactions of cytochrome c isolated from ischemic and control hearts
drug development
-
possibility of nonspecific peroxidation of various substances catalyzed by cytochrome oxidase via the peroxidase mechanism, which may contribute to intracellular metabolism of biologically active drugs (under conditions of cardiotoxicity) and other compounds
drug development
-
tumor necrosis factor alpha-mediated CcO inhibition leads to tissue dysoxia, which suppresses aerobic ATP production and causes a shift to the glycolytic pathway. Kinases and phosphatases involved in reversible tumor necrosis factor alpha-mediated CcO phosphorylation may be promising targets for drug development because they act on an end point of cell signaling
medicine
-
at therapeutic concentrations used for asthma relief, theophylline causes inhibition of the lung enzyme and decreases cellular ATP levels, suggesting a mechanism for its clinical action
medicine
P00395
A122T, i.e. m.6267G>A is a recurrent missense mutation in mitochondrially encoded cytochrome oxidase I specifically associated with cancer
medicine
-
amyloid beta which is involved in Alzheimers disease, specifically inhibits cytochrome-c oxidase
medicine
-
enzyme isoform cytochrome oxifdase III interacts with hepatitis B virus X protein
medicine
-
in skeletal muscle and brain of patients with mutations in genes SCO2 or SURF1, cytochrome-c oxidase holoenzyme is reduced to 10-20%, and to 10-30% in heart, whereas liver contains normal levels of enzyme. Heart, brain, and skeletal muscle of patients contain accumulated levels of enzyme subcomplexes of different subunits, but lacking subunit COX2. SCO2 is presumably involved in formation of the CuA centre of the COX2 subunit, and the lack of the CuA centre may result in decreased stability of COX2
medicine
-
COX deficiency is a common cause of human mitochondrial disease
medicine
-
cytochrome oxidase deficiency is a result of heme deficiency that may be relevant to the demyelinating phenotype of the neurodegenerative disease Friedreich's ataxia. Heme-based stimulation of ironsulfur cluster biogenesis is a rational strategy for the neurodegenerative disease Friedreich's ataxia
medicine
-
evidence of secondary loss of electron transport chain function (loss of complex II-III activity) resulting from a primary electron transport chain deficiency (of complex IV), which provides a possible mechanism for the progressive nature of mitochondrial encephalomyopathies and why in some patients multiple patterns of electron transport chain deficiencies may be demonstrated
medicine
-
simultaneous decrease in 2-deoxyglucose uptake and increase in COI mRNA expression are difficult to reconcile with the current model of basal ganglia function and suggest that the mechanisms by which high-frequency stimulation of the subthalamic nucleus exerts its clinical benefits are more complex than a simple reversal of abnormal activity in the subthalamic nucleus and its targets
drug development
-
tumor necrosis factor alpha-mediated CcO inhibition leads to tissue dysoxia, which suppresses aerobic ATP production and causes a shift to the glycolytic pathway. Kinases and phosphatases involved in reversible tumor necrosis factor alpha-mediated CcO phosphorylation may be promising targets for drug development because they act on an end point of cell signaling
medicine
-
a single injection of exogenous cytochrome c 24 h post-cecal ligation and puncture repletes mitochondrial substrate levels for up to 72 h, restores myocardial COX activity, and significantly improves survival
medicine
-
CO histochemistry, which reflects neuronal activity, is altered at all levels of the auditory system in Relnrl-Orl mutants (with Orleans mutation, which selectively affects cell migration, cell orientation, and to a more limited extent, cell number in the brain tissue)
medicine
P17665
cytochrome oxidase is a metabolic target of caffeine. Stimulation of Cox activity by caffeine via blockade of A2AR signaling may be an important mechanism underlying the therapeutic benefits of caffeine in Parkinsons disease
medicine
-
myocardial CcOX impairment can underlie CO induced cardiac dysfunction
medicine
-
protein kinase C epsilon is activated by hypoxia, which results in the activation of the mitochondrial protein CytCOx, which can protect the lens from mitochondrial damage under naturally hypoxic conditions observed in this tissue
medicine
Mus musculus C57B6/S129
-
cytochrome oxidase is a metabolic target of caffeine. Stimulation of Cox activity by caffeine via blockade of A2AR signaling may be an important mechanism underlying the therapeutic benefits of caffeine in Parkinsons disease
-
medicine
-
6W/Kg GSM 900MHz microwaves may affect brain metabolism and neuronal activity (cytochrome c oxidase activity) in rats
medicine
-
antipsychotic drugs do not alter COX
medicine
-
cytochrome oxidase is a metabolic target of caffeine. Stimulation of Cox activity by caffeine via blockade of A2AR signaling may be an important mechanism underlying the therapeutic benefits of caffeine in Parkinsons disease
medicine
-
hypoxia synergises with NO from neuronal nitric oxide synthase to induce neuronal death via cytochrome oxidase inhibition causing neuronal depolarisation. Neuronal nitric oxide synthase activity sensitises the cells to hypoxic-inhibition of cytochrome oxidase
medicine
-
in HIV-associated dementia, cortical neurons demonstrate decreased respiration upon HIV-1 neurotoxin trans activator of transcription proteint treatment, consistent with inhibition of the enzyme
medicine
-
lack of energy after traumatic brain injury caused by inhibition of CcO may be an important aspect of trauma pathology
medicine
-
low prenatal Cu intake by dams is the determinant of CCO activity in cardiac mitochondria of 21-d-old offspring and may lead to the assembly of a less-than-fully active holoenzyme
medicine
-
recovery of enhanced cytochrome-c oxidase activity may play a role in ischemic preconditioning protection
medicine
-
relationship between the allosteric ATP-inhibition and phosphorylation of CcO subunit I, which apparently occurs in living cells, but is lost under stress (e.g. hypoxic stress)
additional information
-
cytochrome c oxidase is involved in mercury reduction in Acidithiobacillus ferrooxidans cells. Levels of mercury resistance in Acidithiobacillus ferrooxidans strains correspond well with the levels of mercury resistance of cytochrome c oxidase
additional information
-
mean nucleotide variation within the Steganinae subfamily is 8.1%
additional information
B3SGB7
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
B3SGB2
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
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mean nucleotide variation within the Steganinae subfamily is 8.1%, variation within Amiota spp. is 21.8%
additional information
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Arabidopsis thaliana COX19 genes encode functional homologues of the yeast metal chaperone. Smaller COX19-1 isoform, but not the larger one, is able to restore growth on non-fermentable carbon sources when expressed in a yeast cox19 null mutant. Induction by biotic and abiotic stress factors may indicate a relevant role of this protein in the biogenesis of cytochrome c oxidase to replace damaged forms of the enzyme. COX19 has additional functions besides its participation in COX assembly as, for example, metal transport, detoxification, or general protection against oxidative stress
medicine
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relationship between the allosteric ATP-inhibition and phosphorylation of CcO subunit I, which apparently occurs in living cells, but is lost under stress (e.g. hypoxic stress)
additional information
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permeabilization of the outer mitochondrial membrane during apoptosis functions not just to release cytochrome c but also to maintain it oxidized via cytochrome oxidase, thus maximizing caspase activation
additional information
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simple and rapid isolation of COX by immunocapture
nutrition
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in beef muscles psoas major, longissimus lumborum, superficial semimembranosus, deep semimembranosus, and semitendinosus, comparison of cytochrome c oxidase activity, instrumental and visual colour, metmyoglobin-reducing activity, and total reducing activity. Colour stability among muscles is variable and metmyoglobin-reducing activity is more useful than total reducing activity for explaining the role of reducing activity in muscle-colour stability
additional information
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mean nucleotide variation within the Steganinae subfamily is 8.1%
additional information
B3SGB6
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
Q70TD4
100% homology among cox1 sequences from morphotype 1 (females presenting caudal tips smooth without spines) and morphotype 2 (females presenting caudal tips smooth with spines) of Filaria martis collected from beech martens, thus indicating that the shape of female posterior edge may vary among specimens
additional information
B3SGC4
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
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mean nucleotide variation within the Steganinae subfamily is 8.1%
additional information
B3SGC1
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
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molecular phylogenic analysis based on COXI indicates Gobiocypris rarus belongs to Gobioninae. Comparison of DNA with cDNA shows that RNA editing phenomenon does not occur in the COXI of Gobiocypris rarus
additional information
B3SGC2
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
medicine
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mutations in various mitochondrial enzymes can result in Leigh syndrome, among them cytochrome c oxidase
additional information
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an assembled complex IV helps to maintain complex I (NADH-ubiquinone oxidoreductase) in mammalian cells
additional information
Q94QP4
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
B3SGB5
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
B3SGC0
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
B3SGB4
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
B3SGB9
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
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mean nucleotide variation within the Steganinae subfamily is 8.1%
medicine
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the copper-enzyme cytochrome c oxidase has been indicated as a primary molecular target of mutant copper, zinc superoxide dismutase in familial amyotrophic lateral sclerosis
additional information
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an assembled complex IV helps to maintain complex I (NADH-ubiquinone oxidoreductase) in mammalian cells
additional information
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prion protein may not be involved in regulation of cytochrome c oxidase
drug development
Mus musculus C57BL/6
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tumor necrosis factor alpha-mediated CcO inhibition leads to tissue dysoxia, which suppresses aerobic ATP production and causes a shift to the glycolytic pathway. Kinases and phosphatases involved in reversible tumor necrosis factor alpha-mediated CcO phosphorylation may be promising targets for drug development because they act on an end point of cell signaling
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additional information
B3SGA9
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves
additional information
B3SGC3
the MCOX2e region is unique to unionoidean bivalve male genomes. MCOX2e is functional and is likely the result of a single insertion event that took place over 65 MYA, the predicted transmembrane helices/interhelical loops number, length and position variability likely stems from substitution-based processes rather than the typically implicated insertion/deletion events. MCOX2e has relatively high rates of evolution in its primary and secondary structures. MCOX2e displays evidence suggestive of site-specific positive selection. MCOX2e has an overall pattern of purifying selection that leads to the preservation of the transmembrane helices/interhelical loops and hydrophilic C-terminus tail sub-regions, and the more conserved C-terminus tail (relative to the transmembrane helices/interhelical loops sub-region of MCOX2e) is likely biologically active because it contains functional motifs. MCOX2e may have a novel reproductive function within unionoidean bivalves