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Enzyme Nomenclature
Information on EC 1.17.99.9 - heme a synthase
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1.17.99.9 heme a synthaseIUBMB Comments
Contains a heme b cofactor. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a [2,4]. The electrons produced by the reaction are transferred to a heme b cofactor . However, the electron acceptor that is used to restore the heme b cofactor to its oxidized state is still not known (both a thioredoxin-like protein and menaquinol have been proposed).
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The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
Reaction Schemes
+
+
2
=
+
2
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ape1694
cCtaA
COX15
COX15p
ctaA
HAS
TcCox15
COX15
-
-
-
-
ctaA
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ferroheme i + H2O + acceptor = hydroxyferroheme i + reduced acceptor
(1b)
-
-
-
ferroheme o + H2O + 2 acceptor = ferroheme a + 2 reduced acceptor
(overall reaction)
-
-
-
ferroheme o + H2O + acceptor = ferroheme i + reduced acceptor
(1a)
-
-
-
hydroxyferroheme i = ferroheme a + H2O
(1c), spontaneous
-
-
-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
ferroheme o:acceptor C-81-oxidoreductase (heme a-forming)
Contains a heme b cofactor. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a [2,4]. The electrons produced by the reaction are transferred to a heme b cofactor [6]. However, the electron acceptor that is used to restore the heme b cofactor to its oxidized state is still not known (both a thioredoxin-like protein and menaquinol have been proposed).
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ferroheme i + H2O + acceptor
hydroxyferroheme i + reduced acceptor
the enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group
-
-
?
ferroheme i + H2O + acceptor
hydroxyferroheme i + reduced acceptor
the enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
Aeropyrum pernix ATCC 700893
overall reaction
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + acceptor
ferroheme i + reduced acceptor
the enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group
-
-
?
ferroheme o + H2O + acceptor
ferroheme i + reduced acceptor
the enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
ferroheme o + H2O + 2 acceptor
ferroheme a + 2 reduced acceptor
overall reaction. The enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ferredoxin
-
requirement of ferredoxin and indirectly of ferredoxin reductase in hydroxylation of heme O
-
heme a
between 0.2 and 1.95 mol heme B per mol CtaA polypeptide and up to 0.2 mol heme A per mol enzyme (CtaA)
heme
-
contains 0.2 mol of heme B per mol of polypeptide, and a small amounts of heme A
heme b
between 0.2 and 1.95 mol heme B per mol CtaA polypeptide and up to 0.2 mol heme A per mol enzyme (CtaA)
heme b
two molecules of heme B are bound to the enzyme. Wild-type enzyme contains 54.6 nmol/mg protein. Heme composition of wild-type enzyme hemeB:hemeO:hemeOX:hemeOY is 1.95:0.02:0.03:0. Substitutions of His60 and His126 do not affect heme binding, while His216 and His278 in the carboxy-halves are essential in heme binding
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
intracellular copper levels do not affect the activity of the enzyme
additional information
intracellular copper levels do not affect the activity of the enzyme
additional information
-
intracellular copper levels do not affect the activity of the enzyme
additional information
-
intracellular copper levels do not affect the activity of the enzyme
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Brain Diseases
Phenotypic variability and mutation hotspot in COX15-related Leigh syndrome.
Cardiomyopathies
Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency.
Cardiomyopathy, Hypertrophic
Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into its Function in Eukaryotes.
Cardiomyopathy, Hypertrophic
Leigh syndrome associated with a novel mutation in the COX15 gene.
Cardiomyopathy, Hypertrophic
Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency.
Cardiomyopathy, Hypertrophic
Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy.
Cytochrome-c Oxidase Deficiency
Defects in the biosynthesis of mitochondrial heme c and heme a in yeast and mammals.
Cytochrome-c Oxidase Deficiency
Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy.
Cytochrome-c Oxidase Deficiency
Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency.
Leigh Disease
Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into its Function in Eukaryotes.
Leigh Disease
Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome.
Leigh Disease
Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency.
Leigh Disease
Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency.
Mitochondrial Diseases
Phenotypic variability and mutation hotspot in COX15-related Leigh syndrome.
Neoplasms
Systematic expression analysis of the mitochondrial respiratory chain protein subunits identifies COX5B as a prognostic marker in clear cell renal cell carcinoma.
Nervous System Diseases
Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into its Function in Eukaryotes.
Osteoporosis
Identification of B cells participated in the mechanism of postmenopausal women osteoporosis using microarray analysis.
Pulmonary Disease, Chronic Obstructive
Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease.
Starvation
CtaA of Staphylococcus aureus is required for starvation survival, recovery, and cytochrome biosynthesis.
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the amount of mRNA is significantly lower compared with the other life stages
brenda
the replicative life stages (epimastigotes and amastigotes) show higher TcCox15 levels than the infective and non-replicative stage (trypomastigotes). Two times higher level in epimastigotes than in amastigotes and five times higher level than in trypomastigotes
brenda
-
the replicative life stages (epimastigotes and amastigotes) show higher TcCox15 levels than the infective and non-replicative stage (trypomastigotes). Two times higher level in epimastigotes than in amastigotes and five times higher level than in trypomastigotes
-
brenda
the replicative life stages (epimastigotes and amastigotes) show higher TcCox15 levels than the infective and non-replicative stage (trypomastigotes). Two times higher level in epimastigotes than in amastigotes and five times higher level than in trypomastigotes
brenda
-
the replicative life stages (epimastigotes and amastigotes) show higher TcCox15 levels than the infective and non-replicative stage (trypomastigotes). Two times higher level in epimastigotes than in amastigotes and five times higher level than in trypomastigotes
-
brenda
the replicative life stages (epimastigotes and amastigotes) show higher TcCox15 levels than the infective and non-replicative stage (trypomastigotes). Two times higher level in epimastigotes than in amastigotes and five times higher level than in trypomastigotes
brenda
-
the replicative life stages (epimastigotes and amastigotes) show higher TcCox15 levels than the infective and non-replicative stage (trypomastigotes). Two times higher level in epimastigotes than in amastigotes and five times higher level than in trypomastigotes
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Cox15p is a constituent of the mitochondrial inner membrane
brenda
membrane protein with 8 transmembrane segments
brenda
the deduced protein sequence indicates that the enzyme is a 35-kDa intrinsic membrane protein with seven hydrophobic segments
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
cox15 mutants are blocked in heme A but not heme O biosynthesis
malfunction
overexpression of a non-functional mutant causes a reduction in heme A content. This hindrance in the heme A synthesis provokes a reduction on CcO activity and, in consequence, an impairment on Trypanosoma cruzi survival, proliferation and infectivity
malfunction
-
overexpression of a non-functional mutant causes a reduction in heme A content. This hindrance in the heme A synthesis provokes a reduction on CcO activity and, in consequence, an impairment on Trypanosoma cruzi survival, proliferation and infectivity
-
metabolism
-
heme O hydroxylation, catalyzed by Cox15p is an important regulatory step
metabolism
the enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
metabolism
the enzyme is required for heme A biosynthesis
metabolism
-
the enzyme is involved in biosynthesis of heme A, an obligatory cofactor in eukaryotic cytochrome c oxidase. The enzyme catalyses the conversion of heme o to heme a by two successive hydroxylations of the methyl group at C-8, using water as the oxygen source. The first hydroxylation forms heme i, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme a
-
physiological function
the COX15 protein is essential for the assembly of yeast cytochrome oxidase
physiological function
the enzyme is required for starvation survival, recovery, and cytochrome biosynthesis
physiological function
-
the enzyme is required for starvation survival, recovery, and cytochrome biosynthesis
-
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
homooligomer
multimer
-
Cox15 exhibits homotypic interactions, forming highly stable complexes dependent upon hydrophobic interactions. This multimerization is evolutionarily conserved and independent of heme levels and heme a synthase catalytic activity. Cox15 multimerization is important for heme a biosynthesis and/or transfer to maturing cytochrome c oxidase
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C191A/C197A
C35A/C42A
DELTA211-217
Bacillus subtilis LMT20R is deleted for the ctaA gene and, therefore, completely blocked in heme A synthesis. Plasmid pH216MS is obtained from plasmid pH216M (encoding the mutant CtaA-H216M) and carries a 21 bp deletion in ctaA. The CtaADELTA211-217 variant encoded by pH216MS is active in heme A synthesis and supports assembly of normal levels of cytochrome caa3
E57A
heme content of the mutant enzyme is 62% compared to wild-type enzyme
E57A/H216A
heme content of the mutant enzyme is 28% compared to wild-type enzyme
E57A/H278A
heme content of the mutant enzyme is 42% compared to wild-type enzyme
E57Q
heme content of the mutant enzyme is 65% compared to wild-type enzyme
H123A
heme content of the mutant enzyme is 74% compared to wild-type enzyme
H123L
H123M
H123Q
heme content of the mutant enzyme is 64% compared to wild-type enzyme
H216A
heme content of the mutant enzyme is 22% compared to wild-type enzyme
H216A-H278A
heme content of the mutant enzyme is 5% compared to wild-type enzyme
H216M
H216M/DELTA211-217
Bacillus subtilis LMT20R is deleted for the ctaA gene and, therefore, completely blocked in heme A synthesis. Plasmid pH216MS is obtained from plasmid pH216M (encoding the mutant CtaA-H216M) and carries a 21 bp deletion in ctaA. The CtaADELTA211-217 variant encoded by pH216MS is active in heme A synthesis and supports assembly of normal levels of cytochrome caa3
H216Q
heme content of the mutant enzyme is 33% compared to wild-type enzyme
H216Q-H278Q
heme content of the mutant enzyme is 6% compared to wild-type enzyme
H278A
heme content of the mutant enzyme is 56% compared to wild-type enzyme
H278C
heme content of the mutant enzyme is 14% compared to wild-type enzyme
H278M
H278Q
heme content of the mutant enzyme is 15% compared to wild-type enzyme
H60A
heme content of the mutant enzyme is 74% compared to wild-type enzyme
H60A/H123A
heme content of the mutant enzyme is 88% compared to wild-type enzyme
H60M
H60Q
heme content of the mutant enzyme is 65% compared to wild-type enzyme
H60Q-H123Q
heme content of the mutant enzyme is 83% compared to wild-type enzyme
Q103A
heme content of the mutant enzyme is 82% compared to wild-type enzyme
Q257A
heme content of the mutant enzyme is 78% compared to wild-type enzyme
R217A
heme content of the mutant enzyme is 84% compared to wild-type enzyme
R217Q
heme content of the mutant enzyme is 89% compared to wild-type enzyme
R61A
heme content of the mutant enzyme is 77% compared to wild-type enzyme
R61Q
heme content of the mutant enzyme is 79% compared to wild-type enzyme
W39A
heme content of the mutant enzyme is 84% compared to wild-type enzyme
DELTA211-217
-
Bacillus subtilis LMT20R is deleted for the ctaA gene and, therefore, completely blocked in heme A synthesis. Plasmid pH216MS is obtained from plasmid pH216M (encoding the mutant CtaA-H216M) and carries a 21 bp deletion in ctaA. The CtaADELTA211-217 variant encoded by pH216MS is active in heme A synthesis and supports assembly of normal levels of cytochrome caa3
-
E57A
-
heme content of the mutant enzyme is 62% compared to wild-type enzyme
-
H123A
-
heme content of the mutant enzyme is 74% compared to wild-type enzyme
-
H216M
H216M/DELTA211-217
-
Bacillus subtilis LMT20R is deleted for the ctaA gene and, therefore, completely blocked in heme A synthesis. Plasmid pH216MS is obtained from plasmid pH216M (encoding the mutant CtaA-H216M) and carries a 21 bp deletion in ctaA. The CtaADELTA211-217 variant encoded by pH216MS is active in heme A synthesis and supports assembly of normal levels of cytochrome caa3
-
H278Q
-
heme content of the mutant enzyme is 15% compared to wild-type enzyme
-
H60A
-
heme content of the mutant enzyme is 74% compared to wild-type enzyme
-
H60M
H60Q
-
heme content of the mutant enzyme is 65% compared to wild-type enzyme
-
R217W
-
mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome results in impaired catalytic function, and the mutation affects oligomeric properties of the enzyme. The mutations affects protein folding and heme binding
S344P
-
mutations of COX15 causing single amino acid conversions associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome results in impaired stability. The mutations affect protein folding and heme binding
H129A
overexpression of the non-functional TcCox15 mutants causes a negative effect over heme A synthesis, affecting the function of the CcO complex and proliferation of epimastigotes
H206A
overexpression of the non-functional TcCox15 mutants causes a negative effect over heme A synthesis, affecting the function of the CcO complex and proliferation of epimastigotes
H307A
overexpression of the non-functional TcCox15 mutants causes a negative effect over heme A synthesis, affecting the function of the CcO complex and proliferation of epimastigotes
H129A
-
overexpression of the non-functional TcCox15 mutants causes a negative effect over heme A synthesis, affecting the function of the CcO complex and proliferation of epimastigotes
-
H206A
-
overexpression of the non-functional TcCox15 mutants causes a negative effect over heme A synthesis, affecting the function of the CcO complex and proliferation of epimastigotes
-
H307A
-
overexpression of the non-functional TcCox15 mutants causes a negative effect over heme A synthesis, affecting the function of the CcO complex and proliferation of epimastigotes
-
additional information
-
mutations in COX15 repress heme O synthesis and have a dominant effect when combined with other mutations
C191A/C197A
the heme content is reduced to a half of the wild-type level
C35A/C42A
heme content of the mutant enzyme is 77% compared to wild-type enzyme
H216M
heme content of the mutant enzyme is 37% compared to wild-type enzyme
H216M
the H216M variant binds the enzyme substrate heme O, probably with methionine as an axial ligand, but is defective in heme A synthesis and accumulates a mono-hydroxylated reaction intermediate, heme I
H216M
the variant has a decreased heme A synthase activity. It contains heme B, heme O, and heme I, as well as trace amounts of heme A
H278M
heme content of the mutant enzyme is 40% compared to wild-type enzyme
H60M
the mutant enzyme contains heme B and heme A at levels comparable to that of wild-type enzyme
H216M
-
the H216M variant binds the enzyme substrate heme O, probably with methionine as an axial ligand, but is defective in heme A synthesis and accumulates a mono-hydroxylated reaction intermediate, heme I
-
H216M
-
the variant has a decreased heme A synthase activity. It contains heme B, heme O, and heme I, as well as trace amounts of heme A
-
H60M
-
the mutant enzyme contains heme B and heme A at levels comparable to that of wild-type enzyme
-
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
intracellular copper levels do not affect the stability of the enzyme
intracellular copper levels do not affect the stability of the enzyme
-
intracellular copper levels do not affect the stability of the enzyme
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OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the stability of Cox15 is not decreased in the absence of cytochrome c oxidase
-
759467
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli BL21 cells. Heme O synthase and heme A synthase heterologously expressed in Escherichia coli form a complex in vivo
expression in Escherichia coli. Bacillus stearothermophilus CtaA produced in Escherichia coli catalyzes the conversion of heme O to heme A in vitro
heterologously expressed in Escherichia coli
expression in Escherichia coli BL21 cells. Heme O synthase and heme A synthase heterologously expressed in Escherichia coli form a complex in vivo
-
expression in Escherichia coli BL21 cells. Heme O synthase and heme A synthase heterologously expressed in Escherichia coli form a complex in vivo
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transcription of COX15 is positively regulated by by Hap1, a transcription factor whose activity is positively controlled by intracellular heme concentration. While COX15 mRNA levels increase with increasing intracellular heme levels in the presence of Hap1, the mRNA levels of COX15 are depressed and independent of intracellular heme levels in the absence of Hap1
transcription of COX15 is positively regulated by by Hap1, a transcription factor whose activity is positively controlled by intracellular heme concentration. While COX15 mRNA levels increase with increasing intracellular heme levels in the presence of Hap1, the mRNA levels of COX15 are depressed and independent of intracellular heme levels in the absence of Hap1
-
transcription of COX15 is positively regulated by by Hap1, a transcription factor whose activity is positively controlled by intracellular heme concentration. While COX15 mRNA levels increase with increasing intracellular heme levels in the presence of Hap1, the mRNA levels of COX15 are depressed and independent of intracellular heme levels in the absence of Hap1
Saccharomyces cerevisiae W303a
-
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hegg, E.
Biosynthesis and regulation of the heme a biosynthetic pathway
ACS Symp. Ser.
1012
31-46
2009
Bacillus subtilis, Cereibacter sphaeroides
-
brenda
Merli, M.L.; Cirulli, B.A.; Menendez-Bravo, S.M.; Cricco, J.A.
Heme A synthesis and CcO activity are essential for Trypanosoma cruzi infectivity and replication
Biochem. J.
474
2315-2332
2017
Trypanosoma cruzi (V5BC58), Trypanosoma cruzi, Trypanosoma cruzi Dm28c (V5BC58)
brenda
Brown, K.; Allan, B.; Do, P.; Hegg, E.
Identification of novel hemes generated by heme A synthase Evidence for two successive monooxygenase reactions
Biochemistry
41
10906-10913
2002
Bacillus subtilis (P12946), Bacillus subtilis, Bacillus subtilis 168 (P12946)
brenda
Brown, B.M.; Wang, Z.; Brown, K.R.; Cricco, J.A.; Hegg, E.L.
Heme O synthase and heme A synthase from Bacillus subtilis and Rhodobacter sphaeroides interact in Escherichia coli
Biochemistry
43
13541-13548
2004
Bacillus subtilis, Cereibacter sphaeroides (Q3IXW9), Cereibacter sphaeroides, Cereibacter sphaeroides ATCC 17023 (Q3IXW9)
brenda
Brown, K.; Brown, B.; Hoagland, E.; Mayne, C.; Hegg, E.
Heme A synthase does not incorporate molecular oxygen into the formyl group of heme A
Biochemistry
43
8616-8624
2004
Bacillus subtilis (P12946), Bacillus subtilis 168 (P12946)
brenda
Morrison, M.; Cricco, J.; Hegg, E.
The biosynthesis of heme O and heme A is not regulated by copper
Biochemistry
44
12554-12563
2005
Bacillus subtilis, Saccharomyces cerevisiae, Cereibacter sphaeroides (Q3IXW9), Cereibacter sphaeroides, Cereibacter sphaeroides ATCC 17023 (Q3IXW9)
brenda
Hederstedt, L.
Heme A biosynthesis
Biochim. Biophys. Acta
1817
920-927
2012
Aeropyrum pernix, Saccharomyces cerevisiae, Halobacterium salinarum, Schizosaccharomyces pombe, Bacillus subtilis (P12946), Bacillus subtilis 168 (P12946)
brenda
Sakamoto, J.; Hayakawa, A.; Uehara, T.; Noguchi, S.; Sone, N.
Cloning of Bacillus stearothermophilus ctaA and heme a synthesis with the ctaA protein produced in Escherichia coli
Biosci. Biotechnol. Biochem.
63
96-103
1999
Geobacillus stearothermophilus (P94346), Geobacillus stearothermophilus
brenda
Barros, M.H.; Carlson, C.G.; Glerum, D.M.; Tzagoloff, A.
Involvement of mitochondrial ferredoxin and Cox15p in hydroxylation of heme O
FEBS Lett.
492
133-138
2001
Saccharomyces cerevisiae (P40086), Saccharomyces cerevisiae
brenda
Barros, M.; Tzagoloff, A.
Regulation of the heme A biosynthetic pathway in Saccharomyces cerevisiae
FEBS Lett.
516
119-123
2002
Saccharomyces cerevisiae
brenda
Lewin, A.; Hederstedt, L.
Compact archaeal variant of heme A synthase
FEBS Lett.
580
5351-5356
2006
Aeropyrum pernix (Q9YBA3), Aeropyrum pernix, Aeropyrum pernix ATCC 700893 (Q9YBA3)
brenda
Lewin, A.; Hederstedt, L.
Promoted evolution of a shortened variant of heme A synthase in the membrane of Bacillus subtilis
FEBS Lett.
582
1330-1334
2008
Bacillus subtilis (P12946), Bacillus subtilis, Bacillus subtilis 168 (P12946)
brenda
Buchensky, C.; Almirn, P.; Mantilla, B.; Silber, A.; Cricco, J.
The Trypanosoma cruzi proteins TcCox10 and TcCox15 catalyze the formation of heme A in the yeast Saccharomyces cerevisiae
FEMS Microbiol. Lett.
312
133-141
2010
Trypanosoma cruzi (Q4DTN9), Trypanosoma cruzi
brenda
Svensson, B.; Hederstedt, L.
Bacillus subtilis CtaA is a heme-containing membrane protein involved in heme A biosynthesis
J. Bacteriol.
176
6663-6671
1994
Bacillus subtilis
brenda
Clements, M.; Watson, S.; Poole, R.; Foster, S.
CtaA of Staphylococcus aureus is required for starvation survival, recovery, and cytochrome biosynthesis
J. Bacteriol.
181
501-507
1999
Staphylococcus aureus (Q2G2C0), Staphylococcus aureus, Staphylococcus aureus NCTC 8325 (Q2G2C0)
brenda
Hederstedt, L.; Lewin, A.; Throne-Holst, M.
Heme A synthase enzyme functions dissected by mutagenesis of Bacillus subtilis CtaA
J. Bacteriol.
187
8361-8369
2005
Bacillus subtilis (P12946), Bacillus subtilis, Bacillus subtilis 168 (P12946)
brenda
Mogi, T.
Probing structure of heme A synthase from Bacillus subtilis by site-directed mutagenesis
J. Biochem.
145
625-633
2009
Bacillus subtilis (P12946), Bacillus subtilis, Bacillus subtilis 168 (P12946)
brenda
Glerum, D.M.; Muroff, I.; Jin, C.; Tzagoloff, A.
COX15 codes for a mitochondrial protein essential for the assembly of yeast cytochrome oxidase
J. Biol. Chem.
272
19088-19094
1997
Saccharomyces cerevisiae (P40086), Saccharomyces cerevisiae
brenda
Barros, M.; Nobrega, F.; Tzagoloff, A.
Mitochondrial ferredoxin is required for heme a synthesis in Saccharomyces cerevisiae
J. Biol. Chem.
277
9997-10002
2002
Saccharomyces cerevisiae
brenda
Wang, Z.; Wang, Y.; Hegg, E.L.
Regulation of the heme A biosynthetic pathway differential regulation of heme A synthase and heme O synthase in Saccharomyces cerevisiae
J. Biol. Chem.
284
839-847
2009
Saccharomyces cerevisiae, Saccharomyces cerevisiae W303a
brenda
Swenson, S.; Cannon, A.; Harris, N.J.; Taylor, N.G.; Fox, J.L.; Khalimonchuk, O.
Analysis of oligomerization properties of heme a synthase provides insights into its function in eukaryotes
J. Biol. Chem.
291
10411-10425
2016
Saccharomyces cerevisiae
brenda
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EXTERNAL LINKS (specific for EC-Number 1.17.99.9)
Transporter Classification Database (TCDB): 3.D.4.4.1
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Release 2023.1 (January 2023)
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