4.4.1.17: Holocytochrome-c synthase
This is an abbreviated version!
For detailed information about Holocytochrome-c synthase, go to the full flat file.
Word Map on EC 4.4.1.17
Reaction
Synonyms
CCHL, ccsA1, cyc2p, CYC3, cytochrome c heme lyase, Cytochrome c heme-lyase, Cytochrome c synthase, HCC synthase, HCCH, HCCS, heme lyase, holocytochrome c synthase, Holocytochrome c synthetase, Holocytochrome c-type synthase, Holocytochrome-C synthase, Holocytochrome-C-type synthase, Synthetase, holocytochrome c, System III
ECTree
4.4.1.17 Holocytochrome-c synthaseAdvanced search results
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Substrates Products on EC 4.4.1.17 - Holocytochrome-c synthase
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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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?
