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Information on EC 4.4.1.17 - Holocytochrome-c synthase
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4.4.1.17 Holocytochrome-c synthaseIUBMB Comments
In the reverse direction, the enzyme catalyses the attachment of heme to two cysteine residues in the protein, forming thioether links.
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Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
system iii, heme lyase, cytochrome c heme lyase, cyc2p, holocytochrome c synthase, holocytochrome c-type synthase, ccsa1, holocytochrome c synthetase, cytochrome c synthase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CCHL
cytochrome c heme lyase
Cytochrome c heme-lyase
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Cytochrome c synthase
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HCCS
holocytochrome c synthase
Holocytochrome c synthetase
Holocytochrome c-type synthase
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Holocytochrome-C synthase
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Holocytochrome-C-type synthase
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Synthetase, holocytochrome c
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CCHL
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Holocytochrome c synthetase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Holocytochrome c = apocytochrome c + heme
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
covalent attachment of heme
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SYSTEMATIC NAME
IUBMB Comments
holocytochrome-c apocytochrome-c-lyase (heme-forming)
In the reverse direction, the enzyme catalyses the attachment of heme to two cysteine residues in the protein, forming thioether links.
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CAS REGISTRY NUMBER
COMMENTARY
75139-03-6
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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
apo-iso-1 cytochrome c + heme
holocytochrome c
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single residue variants of five conserved N-terminal residues G6A, K10A, G11A, F15A and R18A of Saccharomyces cerevisiae iso-1 cytochrome c. F15A replacement, corresponding to F10 in the horse cytochrome c, is not matured at all. G6A, K10A, G11A, and R18A variants are matured
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?
apo-MccA + heme
holo-MccA
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MccA contains seven conventional heme-binding motifs and a CX15CH sequence involved in binding of an additional heme catalyzed by a specific lyase enzyme
octaheme protein
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?
Apocytochrome c + heme
?
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enzyme for the covalent attachment of heme to apocytochrome c
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?
Apocytochrome c + heme
Holocytochrome c
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reaction is catalyzed by a complex formed by two enzymes: CcmF and CcmH
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?
Apocytochrome c + heme
Holocytochrome c
conserved His154 is the key ligand to the heme iron, formation of the enzyme-heme complex serves as the platform for interaction with apocytochrome c, the heme is the central molecule mediating contact between enzyme and apocytochrome c. Conserved His19 of the CXXCH motif in apocytochrome c supplies the second axial ligand to heme in the trapped enzyme-heme-cytochrome c complex. Molecular mechanisms, overview
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?
Apocytochrome c + heme
Holocytochrome c
the catalytic function of the enzyme depends on its ability to coordinate interactions between its substrates: heme and cytochrome c, four-step model describing enzyme-mediated cytochrome c assembly, identifying conserved histidine residue 154 as an axial ligand to the heme iron, overview. The enzyme contains two heme-binding domains, heme contacts mediated by residues within these domains modulate the dynamics of heme binding and contribute to the stability of the enzyme-heme-cytochrome c steady state ternary complex. While some residues are essential for initial heme binding, others impact the subsequent release of the holocytochrome c product
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?
Apocytochrome c + heme
Holocytochrome c
the enzyme attaches heme to wild-type cytochrome, and to mutant cytochromes containing individual cysteine, histidine, and double cysteine of conserved motif CXXCH, but not the mutant with triple cysteine/histidine substitutions, overview. His19 in cytochrome c is important for 1. to provide the second axial ligand to the heme iron in preparation for covalent attachment, 2. to spatially position the two cysteinyl sulfurs adjacent to the two heme vinyl groups for thioether formation, and 3. to aid in release of the holocytochrome c from the enzyme's active site. Substitutions of His19 in cytochrome c to seven other residues (G,A,M,R,K,C,Y) show that only mutant H19M is able to carry out these three roles, albeit at lower efficiencies than the wild-type His19. The histidine in the CXXCH motif acts as an axial ligand to the heme iron
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?
Apocytochrome c + heme
Holocytochrome c
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catalyzes covalent attachment of heme group to two cysteine residues in the protein
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?
Apocytochrome c + heme
Holocytochrome c
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catalyzes covalent attachment of heme group to two cysteine residues in the protein
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?
Apocytochrome c + heme
Holocytochrome c
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chimeric substrate comprising a short Saccharomyces cerevisiae mitochondrial cytochrome c N-terminal region plus the C-terminal sequence, including the CXXCH heme-binding motif, of Paracoccus denitrificans cytochrome c that is not otherwise processed by HCCS. Saccharomyces cerevisiae HCCS is able to attach heme to the chimeric protein
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?
Apocytochrome c + heme
Holocytochrome c
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chorse cytochrome c, recombinant substrate with mutations D2A, E4A, K5A, G6A, K7A, K8A and F10A. For the D2A, E4A and K7A variants, heme attachment is not attenuated by the amino acid replacements. The G6A and F10A variants are not matured at detectable levels.K5A and K8A variants of horse cytochrome c are also matured at similar levels to the wild type protein
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?
Apocytochrome c + heme
Holocytochrome c
activity of the recombinant enzyme with several mutant variants of holocytochrome c552 from Hydrogenobacter thermophilus coexpressed in Escherichia coli in cytoplasm and periplasm, respectively, and enzyme activity with several cytocohrome variants from Equus caballus in Escherichia coli cells, heme attachment motifs, overview
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?
Apocytochrome c + heme
Holocytochrome c
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Equus caballus heart cytochrome c or Strep-tagged Saccharomyces cerevisiae cytochrome c are coexpressed in Escherichia coli strain BL21(DE3) with Saccharomyces cerevisiae holocytochrome c synthase. No product synthesis from truncated cytochrome c1 mutants G29X, H45X and K60X, with the X indicating the position of the inserted stop codon
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?
apocytochrome c1 + heme
holocytochrome c1
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apocytochrome c1 mutant with a CAPCH heme-binding site instead of the wild-type CAACH is substrate of holocytochrome-c synthase and strictly dependent upon the presence of putative redox protein Cyc2p for assembly. The identity of the second intervening residue in the CXXCH motif is the key in determining the holocytochrome-c synthase-dependent versus holocytochrome-c1 synthase-dependent assembly of holocytochrome c1
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?
additional information
?
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substrate specificity of the human enzyme, overview. Engineering of a bacterial cytochrome c into a robust substrate for the human enzyme, overview
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?
additional information
?
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substrate specificity of the human enzyme, overview. Engineering of a bacterial cytochrome c into a robust substrate for the human enzyme, overview
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?
additional information
?
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HCCS mediates heme attachment to the N-terminal cysteine in cytochrome c C-terminal variants, but up to 50% of the cytochrome c produced is modified in an oxygen-dependent manner, resulting in a mixed population of cytochrome c. Natural HCCS-mediated heme attachment to C-terminal cytochrome variants likely initiates at the C-terminal cysteine
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?
additional information
?
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during apoptotic stimuli, enzyme translocates to outside the mitochondria, and binds to and suppresses the X-linked inhibitor of apoptosis protein XIAP, leading to activation of caspase-3. The N-terminus of the neuronal glutamate transporter excitatory amino-acid carrier 1 EAAC1 can bind to enzyme which interferes with the enzyme-XIAP association
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?
additional information
?
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distinct from apocytochrome c binding protein
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?
additional information
?
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Saccharomyces cerevisiae has another, similar enzyme: cytochrome-c1-heme lyase
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?
additional information
?
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no activity with cytochrome c1
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?
additional information
?
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the CXXCH motif and the N-terminus of the apocytochrome polypeptide are important protein-protein recognition motifs in enzyme-substrate interaction, the N-terminal region of the mitochondrial cytochrome c sequence is critical for attachment of heme to apocytochrome c
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?
additional information
?
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the enzyme shares the ability of CCM, i.e. System I, the cytochrome c maturation system, found in many bacteria and commonly employed in the maturation of bacterial cytochromes c in Escherichia coli-based expression systems, to mature hemes c with extended heme attachment motifs, comparison of System I and cytochrome c heme lyase, i.e. System III, substrate specificities, overview
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?
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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
additional information
?
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during apoptotic stimuli, enzyme translocates to outside the mitochondria, and binds to and suppresses the X-linked inhibitor of apoptosis protein XIAP, leading to activation of caspase-3. The N-terminus of the neuronal glutamate transporter excitatory amino-acid carrier 1 EAAC1 can bind to enzyme which interferes with the enzyme-XIAP association
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?
Apocytochrome c + heme
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enzyme for the covalent attachment of heme to apocytochrome c
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?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-ethylmaleimide
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kinetics, in vivo; pretreatment of reticulocyte lysates with N-ethylmaleimide results in nearly complete inactivation
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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independent of a potential across the inner mitochondrial membrane generated by N,N,N',N'-tetramethyl-p-phenylenediamine/ascorbate
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
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Km values for holocytochrome c using mitochondria and mitoplasts from several yeast strains
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
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activity is independent of a potential across the inner mitochondrial membrane generated by N,N,N',N'-tetramethyl-p-phenylenediamine/ascorbate, requires an unidentified cytosolic factor
additional information
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enzyme activity increases after solubilization from the membrane with Triton X-100
additional information
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method for determination of activity by HPLC
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene CaCYC3, 45% homology to the gene CYC3 of Saccharomyces cerevisiae
SwissProt
brenda
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SwissProt
brenda
female patients with microphthalmia with linear skin defects syndrome, i.e. MLS or MIDAS
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brenda
possibly associated with microphtalmia with linear skin defects syndrome
SwissProt
brenda
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brenda
baker's yeast, strain D311-3A or B-7034 and cyc3-multi-copy mutant strain B-6868-1
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brenda
strain D311-3A or B-7034, and cyc3-multi-copy mutant strain B-6868-1
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brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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integral membrane protein, facing cytoplasmic surface
brenda
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separation of mitochondrial inner and outer membrane on a sucrose gradient
brenda
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novel, non-conservative import pathway: the enzyme precursor is translocated into mitochondria using the MOM19-GIP receptor complex in the outer membrane, independent of ATP-hydrolysis and electrochemical potential as external energy source
brenda
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enzyme is transported into the intermembrane space via a direct sorting pathway, that can occur in absence of external energy sources
brenda
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during apoptotic stimuli, enzyme translocates to outside the mitochondria, and binds to and suppresses the X-linked inhibitor of apoptosis protein XIAP, leading to activation of caspase-3. The N-terminus of the neuronal glutamate transporter excitatory amino-acid carrier 1 EAAC1 can bind to enzyme which interferes with the enzyme-XIAP association
brenda
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novel, non-conservative import pathway: the enzyme precursor is translocated into mitochondria using the MOM19-GIP receptor complex in the outer membrane, independent of ATP-hydrolysis and electrochemical potential as external energy source
brenda
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integral membrane protein of inner membrane (facing cytoplasmic surface)
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
at least five heme c maturation systems have been identified: Systems I, II, III, IV, and V. System I, the cytochrome c maturation (CCM) system, involves genes ccmA-H5 and is found in various bacteria and in plant mitochondria. System I matures cytochromes c in the periplasmic space of bacteria. System II, cytochrome c synthesis (CCS), consists of four modular components and occurs in various bacteria as well as the thylakoid membranes of plants and algae. System III, also called cytochrome c heme lyase (CCHL), is a single enzyme found in the mitochondria of fungi, vertebrates and invertebrates
metabolism
the enzyme is the primary component of the eukaryotic cytochrome c biogenesis pathway, known as System III
physiological function
additional information
physiological function
C-type cytochromes are distinguished by the covalent attachment of a heme cofactor, a modification that is typically required for its subsequent folding, stability, and function. Heme attachment takes place in the mitochondrial intermembrane space and, in most eukaryotes, is mediated by holocytochrome c synthase
physiological function
cytochrome c, an essential electron carrier in mitochondria and a critical component of the apoptotic pathway, contains a heme cofactor covalently attached to the protein at a conserved CXXCH motif requiring the mitochondrial protein holocytochrome c synthase
physiological function
for mitochondrial cytochrome c assembly, the enzyme binds heme and apocytochrome c substrate to catalyze a covalent attachment of heme by thioether bonds between heme vinyl groups and a conserved CXXCH motif of cytochrome c/c1, and subsequently releases holocytochrome c for proper folding to its native structure, mechanism of assembly, overview
physiological function
human cyts c with deletion of a single residues in helix-1, DELTA M13 cyt c, is poorly matured by human HCCS. Although an HCCS-wild-type cytochrome c complex contains two covalent links, HCCS DELTA M13 cytochrome c contains only one thioether attachment. This attachment is to the second thiol of residues C15SQC18H. The serine residue (of CSQCH) would be anchored where the first cysteine should be in DELTA M13 cytochrome c. An engineered cytochrome c with a CQCH motif in the DELTA M13 background is matured at 2-3fold higher levels
additional information
construction endogenous holocytochrome c mutant variant with a CX3CH motif. The second X residue in the heme binding motif of cyt c1 (CXXCH) is important for its recognition as a substrate by the enzyme
additional information
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the CP motifs, commonly found in heme-binding proteins, are not required for enzyme activity of te Saccharomyyces cerevisiae enzyme, while mutations in the human enzyme on the C-terminal side of the CP motifs cause disease states of microphthalmia with linear skin defects due to abolished or drastically attenuated holocytochrome c production
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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comparison of amino acid sequence of Saccharomyces cerevisiae and Neurospora crassa enzymes to that of Saccharomyces cerevisiae cytochrome-c1-heme lyase
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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the N-terminus of the neuronal glutamate transporter excitatory amino-acid carrier 1 EAAC1 can bind to enzyme
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C15S
the HCCS:cyt c C15S and C18A mutants support the formation of single thioether cross-links between the heme and cyt c at the vinyl position alternate to the mutation
C18A
the HCCS:cyt c C15S and C18A mutants support the formation of single thioether cross-links between the heme and cyt c at the vinyl position alternate to the mutation
DELTA197-268
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mutation identified in female patient with microphthalmia with linear skin defects syndrome. In contrast to wild-type, mutant protein is unable to complement a Saccharomyces cerevisiae mutant deficient in the yeast enzyme ortholog. Upon expression in CHO-K1 cells, mutant protein fails to be sorted to mitochondria. Mutation results in disturbance of both oxidative phosphorylation and the balance between apoptosis and necrosis
E159A
E159D
site-directed mutagenesis of a domain II residue, the mutant shows altered heme binding compared to the wild-type enzyme
E159K
site-directed mutagenesis of a domain II residue, the mutant shows altered heme binding compared to the wild-type enzyme
M130A
site-directed mutagenesis of a domain I residue, the mutant shows altered heme binding compared to the wild-type enzyme
N128A
site-directed mutagenesis of a domain I residue, the mutant shows altered heme binding compared to the wild-type enzyme
N128A/M130A
site-directed mutagenesis of domain I residues, the mutant shows altered heme binding compared to the wild-type enzyme
N155A
site-directed mutagenesis of a domain II residue, the mutant shows altered heme binding compared to the wild-type enzyme
P121A
site-directed mutagenesis of a domain I residue, the mutant shows altered heme binding compared to the wild-type enzyme
R217C
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mutation identified in female patient with microphthalmia with linear skin defects syndrome. In contrast to wild-type, mutant protein is unable to complement a Saccharomyces cerevisiae mutant deficient in the yeast enzyme ortholog. Mutation results in disturbance of both oxidative phosphorylation and the balance between apoptosis and necrosis
W118A
Y120A
site-directed mutagenesis of a domain I residue, the mutant shows altered heme binding compared to the wild-type enzyme
Y120A/P121A
site-directed mutagenesis of domain I residues, the mutant shows altered heme binding compared to the wild-type enzyme
C15A
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site-directed mutagenesis, cytoplasm-targeted mutant, the mutant is matured and undergoes heme attachment like the wild-type enzyme
C18A
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site-directed mutagenesis, cytoplasm-targeted mutant, the mutant does not undergo heme attachment
C26A
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site-directed mutagenesis of CP-motif 1 of the enzyme, the mutant shows activity similar to the wild-type enzyme
C26A/C42A
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site-directed mutagenesis of both CP-motifs of the enzyme, the mutant shows activity similar to the wild-type enzyme
C26A/P27A
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site-directed mutagenesis of CP-motif 1 of the enzyme, the mutant shows activity similar to the wild-type enzyme
C42A
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site-directed mutagenesis of CP-motif 2 of the enzyme, the mutant shows activity similar to the wild-type enzyme
C42A/P43A
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site-directed mutagenesis of CP-motif 2 of the enzyme, the mutant shows activity similar to the wild-type enzyme
E133A
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site-directed mutagenesis, the mutant shows highly reduced activity compared with the wild-type enzyme
E133K
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site-directed mutagenesis, the mutant shows highly reduced activity compared with the wild-type enzyme
F15A
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site-directed mutagenesis, periplasm-targeted mutant, the mutant variant does not produce holocytochrome c
F15E
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site-directed mutagenesis, periplasm-targeted mutant, the mutant variant does not produce holocytochrome c
F15I
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site-directed mutagenesis, periplasm-targeted mutant, the mutant shows reduced holocytochrome c production compared to the wild-type enzyme
F15W
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site-directed mutagenesis, periplasm-targeted mutant, the mutant shows reduced holocytochrome c production compared to the wild-type enzyme
F15Y
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site-directed mutagenesis, periplasm-targeted mutant, the mutant shows unaltered holocytochrome c production like the wild-type enzyme
H19K
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site-directed mutagenesis, cytoplasm-targeted mutant, the mutant does not undergo heme attachment
H19M
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site-directed mutagenesis, cytoplasm-targeted mutant, the mutant does not undergo heme attachment
H19R
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site-directed mutagenesis, cytoplasm-targeted mutant, the mutant does not undergo heme attachment
additional information
E159A
site-directed mutagenesis of a domain II residue, the mutant shows altered heme binding compared to the wild-type enzyme
E159A
mutant displays enhanced release of cytochrome c from the active site. The mutant allows for synthesis of cytochrome c variants such as cyt c H19M (bis-Met), cyt c M81H (bis-His), cyt c M81A (His/OH?), cyt c C15S which exhibit proper folding
W118A
site-directed mutagenesis of a domain I residue, the mutant shows altered heme binding compared to the wild-type enzyme
W118A
mutant displays enhanced release of cytochrome c from the active site. The mutant allows for synthesis of cytochrome c variants such as cyt c H19M (bis-Met), cyt c M81H (bis-His), cyt c M81A (His/OH), cyt c C15S which exhibit proper folding
additional information
the mutants show altered heme binding with and/or without presence of cytochrome c, overview
additional information
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the mutants show altered heme binding with and/or without presence of cytochrome c, overview
additional information
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construction of T17, K16, G29, H45, and K60 deletion mutants and of a mutant with periplasmic targeting sequence
additional information
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in enzyme deletion mutant, maturation of c-type cytochromes produced under fumarate- and nitrate-respiring conditions is not affected. The mutant grows normally by respiratory nitrate ammonification with formate as electron donor. Cytochrome c protein MccA is not detectable by heme staining in mutant cells from stationary growth phase. In exponential growth phase, reduced amounts of transiently formed MccA are detectable
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged enzyme and cytochrome c mutants from Escherichia coli strain RK103 membranes by ultracentrifugation, glutahione affinity chromatographyand ultrafiltration
recombinant GST-tagged wild-type and mutant enzymes and cytochrome c from Escherichia coli strain RK103 membranes by ultracentrifugation, glutahione affinity chromatographyand ultrafiltration
wild-type membrane-bound human GST-tagged enzyme with endogenous heme and in complex with its cognate human apocytochrome c and mutants from Escherichia coli
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning in Escherichia coli
coexpression of N-terminally GST-tagged wild-type enzyme with endogenous heme and in complex with its cognate human apocytochrome c and mutants in Escherichia coli
coexpression of the wild-type enzyme with periplasmic targeting sequence and addition of the Pseudomonas aeruginosa cytochrome c551/552 pre-sequence, and mutant enzymes with Equus caballus heart cytochrome c or Strep-tagged Saccharomyces cerevisiaecytochrome c in Escherichia coli strain BL21(DE3)
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expression in Escherichia coli
expression of the enzyme in Escherichia coli cytosplasm, coexpression with several mutant variants of holocytochrome c552 from Hydrogenobacter thermophilus, the latter are expressed in the periplasm, or several cytochrome c variants from Equus caballus
heterologous expression in a multicopy yeast vector
recombinant coexpression of GST-tagged wild-type and mutant enzymes with cytochrome c in Escherichia coli strain RK103 membranes
recombinant coexpression of the GST-tagged enzyme with cytochrome c mutants, containing individual cysteine, histidine, double cysteine, and triple cysteine/histidine substitutions of conserved motif CXXCH, in Escherichia coli strain RK103 membranes, single and double mutants form a complex with the enzyme but not the triple mutant
recombinant expression of His-tagged wild-type enzyme and mutants in Escherichia coli strain BL21(DE3) cytoplasm, coexpression with Equus caballus cytochrome c
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
molecular biology
system III, cytochrome c heme lyase, is an enzyme found in the mitochondria of many eukaryotes, which is used for heterologous expression of mitochondrial holocytochromes c
synthesis
mutants E159A and W118A display enhanced release of cytochrome c from the active site. The mutant allows for synthesis of cytochrome c variants such as cyt c H19M (bis-Met), cyt c M81H (bis-His), cyt c M81A (His/OH), cyt c C15S, which exhibit proper folding
medicine
-
identification of mutations R217C and DELTA197-268 in female patients with microphthalmia with linear skin defects syndrome. In contrast to wild-type, mutant proteins are unable to complement a Saccharomyces cerevisiae mutant deficient in the yeast enzyme ortholog. Mutation results in disturbance of both oxidative phosphorylation and the balance between apoptosis and necrosis. Upon expression in CHO-K1 cells, mutant DELTA197-268 protein fails to be sorted to mitochondria
medicine
patient with deletion of the HCCS gene, diagnosis of a microphthalmia with linaer skin defects syndrome. Patient showed bilateral microphthalmia with optic atrophy, a congenital cataract, linear vascular lesions on the cheeks, neck and nose, apparently small, cupped poorly formed ears, anteverted nares, small areolae, a prominent xiphoid, an apparently small phallus, and right cryptorchidism. He had a patent ductus arteriosus, a patent foramen ovale and severe pulmonary hypertension attributed to pulmonary hypoplasia. Head ultrasound showed bilateral ventriculomegaly and agenesis of the corpus callosum. He also had poor tone and diminished reflexes on neurological examination. Patient died at 4 days of age
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Enosawa, S.; Ohashi, A.
Localization of enzyme for heme attachment to apocytochrome c in yeast mitochindria
Biochem. Biophys. Res. Commun.
141
1145-1150
1986
Saccharomyces cerevisiae
brenda
Dumont, M.; Ernst, J.F.; Hampsey, D.M.; Sherman, F.
Identification and sequence of the gene encoding cytochrome c heme lyase in the yeast Sacchomyces cerevisiae
EMBO J.
6
235-241
1987
Saccharomyces cerevisiae
brenda
Nicholson, D.W.; Khler, H.; Neupert, W.
Import of cytochrome c into mitochondria. Cytochrome c heme lyase
Eur. J. Biochem.
164
147-157
1987
Neurospora crassa
brenda
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Import of cytochrome c heme lyase into mitochondria: a novel pathway into the intermembarne space
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Neurospora crassa
brenda
Zollner, A.; Rdel, G.; Haid, A.
Molecular cloning and characterization of the Saccharomyces cerevisiae CYT2 gene encoding cytochrome-c1-heme lyase
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Saccharomyces cerevisiae, Neurospora crassa
brenda
Drygas, M.E.; Lambowitz, A.M.; Nargang, F.E.
Cloning and analysis of the Neurospora crassa gene for cytochrome c heme lyase
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brenda
Schaefer, L.; Ballabio, A.; Zoghbi, H.Y.
Cloning and characterization of a putative human holocytochrome c-type synthetase gene (HCCS) isolated from the critical region for microphthalmia with linear skin defects (MLS)
Genomics
34
166-172
1996
Homo sapiens (P53701), Mus musculus (P53702)
brenda
Steiner, H.; Zollner, A.; Haid, A.; Neupert, W.; Lill, R.
Biogenesis of mitochondrial heme lyases in yeast. Import and folding in the intermembrane space
J. Biol. Chem.
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Saccharomyces cerevisiae
brenda
Tong, J.; Margoliash, E.
Cytochrome c heme lyase activity of yeast mitochondria
J. Biol. Chem.
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Saccharomyces cerevisiae
brenda
Ren, Q.; Ahuja, U.; Thony-Meyer, L.
A bacterial cytochrome c heme lyase. CcmF forms a complex with the heme chaperone CcmE and CcmH but not with apocytochrome c
J. Biol. Chem.
277
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Escherichia coli
brenda
Bernard, D.G.; Gabilly, S.T.; Dujardin, G.; Merchant, S.; Hamel, P.P.
Overlapping specificities of the mitochondrial cytochrome c and c1 heme lyases
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Homo sapiens (P53701), Homo sapiens, Mus musculus (P53702), Saccharomyces cerevisiae
brenda
Cervera, A.M.; Gozalbo, D.; McCreath, K.J.; Gow, N.A.R.; Martinez, J.P.; Casanova, M.
Molecular cloning and characterization of a Candida albicans gene coding for cytochrome c heme lyase and a cell wall-related protein
Mol. Microbiol.
30
67-81
1998
Candida albicans (P53700)
brenda
Bernard, D.G.; Quevillon-Cheruel, S.; Merchant, S.; Guiard, B.; Hamel, P.P.
Cyc2p, a membrane-bound flavoprotein involved in the maturation of mitochondrial c-type cytochromes
J. Biol. Chem.
280
39852-39859
2005
Saccharomyces cerevisiae
brenda
Wimplinger, I.; Morleo, M.; Rosenberger, G.; Iaconis, D.; Orth, U.; Meinecke, P.; Lerer, I.; Ballabio, A.; Gal, A.; Franco, B.; Kutsche, K.
Mutations of the mitochondrial holocytochrome c-type synthase in X-linked dominant microphthalmia with linear skin defects syndrome
Am. J. Hum. Genet.
79
878-889
2006
Homo sapiens
brenda
Kiryu-Seo, S.; Gamo, K.; Tachibana, T.; Tanaka, K.; Kiyama, H.
Unique anti-apoptotic activity of EAAC1 in injured motor neurons
EMBO J.
25
3411-3421
2006
Mus musculus
brenda
Hartshorne, R.S.; Kern, M.; Meyer, B.; Clarke, T.A.; Karas, M.; Richardson, D.J.; Simon, J.
A dedicated haem lyase is required for the maturation of a novel bacterial cytochrome c with unconventional covalent haem binding
Mol. Microbiol.
64
1049-1060
2007
Wolinella succinogenes
brenda
Kemmer, D.; McHardy, L.M.; Hoon, S.; Reberioux, D.; Giaever, G.; Nislow, C.; Roskelley, C.D.; Roberge, M.
Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis
BMC Microbiol.
9
9-9
2009
Saccharomyces cerevisiae
brenda
Drenckhahn, J.D.; Schwarz, Q.P.; Gray, S.; Laskowski, A.; Kiriazis, H.; Ming, Z.; Harvey, R.P.; Du, X.J.; Thorburn, D.R.; Cox, T.C.
Compensatory growth of healthy cardiac cells in the presence of diseased cells restores tissue homeostasis during heart development
Dev. Cell
15
521-533
2008
Mus musculus
brenda
Qidwai, K.; Pearson, D.; Patel, G.; Pober, B.; Immken, L.; Cheung, S.; Scott, D.
Deletions of Xp provide evidence for the role of holocytochrome c-type synthase (HCCS) in congenital diaphragmatic hernia
Am. J. Med. Genet. A
152
1588-1590
2010
Homo sapiens (P53701)
brenda
Stevens, J.M.; Zhang, Y.; Muthuvel, G.; Sam, K.A.; Allen, J.W.; Ferguson, S.J.
The mitochondrial cytochrome c N-terminal region is critical for maturation by holocytochrome c synthase
FEBS Lett.
585
1891-1896
2011
Saccharomyces cerevisiae
brenda
Corvest, V.; Murrey, D.A.; Bernard, D.G.; Knaff, D.B.; Guiard, B.; Hamel, P.P.
c-type cytochrome assembly in Saccharomyces cerevisiae: a key residue for apocytochrome c1/lyase interaction
Genetics
186
561-571
2010
Saccharomyces cerevisiae
brenda
Babbitt, S.E.; San Francisco, B.; Bretsnyder, E.C.; Kranz, R.G.
Conserved residues of the human mitochondrial holocytochrome C synthase mediate interactions with heme
Biochemistry
53
5261-5271
2014
Homo sapiens (P53701), Homo sapiens
brenda
Moore, R.L.; Stevens, J.M.; Ferguson, S.J.
Mitochondrial cytochrome c synthase: CP motifs are not necessary for heme attachment to apocytochrome c
FEBS Lett.
585
3415-3419
2011
Saccharomyces cerevisiae
brenda
Zhang, Y.; Stevens, J.M.; Ferguson, S.J.
Substrate recognition of holocytochrome c synthase: N-terminal region and CXXCH motif of mitochondrial cytochrome c
FEBS Lett.
588
3367-3374
2014
Saccharomyces cerevisiae
brenda
Babbitt, S.E.; San Francisco, B.; Mendez, D.L.; Lukat-Rodgers, G.S.; Rodgers, K.R.; Bretsnyder, E.C.; Kranz, R.G.
Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, CysXXCysHis
J. Biol. Chem.
289
28795-18807
2014
Homo sapiens (P53701), Homo sapiens
brenda
Kleingardner, J.G.; Bren, K.L.
Comparing substrate specificity between cytochrome c maturation and cytochrome c heme lyase systems for cytochrome c biogenesis
Metallomics
3
396-403
2011
Saccharomyces cerevisiae (P06182)
brenda
San Francisco, B.; Bretsnyder, E.C.; Kranz, R.G.
Human mitochondrial holocytochrome c synthases heme binding, maturation determinants, and complex formation with cytochrome c
Proc. Natl. Acad. Sci. USA
110
E788-E797
2013
Homo sapiens (P53701), Homo sapiens
brenda
Babbitt, S.E.; Hsu, J.; Mendez, D.L.; Kranz, R.G.
Biosynthesis of single thioether c-type cytochromes provides insight into mechanisms intrinsic to holocytochrome c synthase (HCCS)
Biochemistry
56
3337-3346
2017
Homo sapiens (P53701)
brenda
Babbitt, S.E.; Hsu, J.; Kranz, R.G.
Molecular basis behind inability of mitochondrial holocytochrome c synthase to mature bacterial cytochromes Defining a critical role for cytochrome c alpha helix-1
J. Biol. Chem.
291
17523-17534
2016
Homo sapiens (P53701), Homo sapiens
brenda
Mendez, D.L.; Babbitt, S.E.; King, J.D.; DAlessandro, J.; Watson, M.B.; Blankenship, R.E.; Mirica, L.M.; Kranz, R.G.
Engineered holocytochrome c synthases that biosynthesize new cytochromes c
Proc. Natl. Acad. Sci. USA
114
2235-2240
2017
Homo sapiens (P53701), Homo sapiens
brenda
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