BRENDA - Enzyme Database
show all sequences of 4.4.1.17

Mechanisms of mitochondrial holocytochrome c synthase and the key roles played by cysteines and histidine of the heme attachment site, CysXXCysHis

Babbitt, S.E.; San Francisco, B.; Mendez, D.L.; Lukat-Rodgers, G.S.; Rodgers, K.R.; Bretsnyder, E.C.; Kranz, R.G.; J. Biol. Chem. 289, 28795-18807 (2014)

Data extracted from this reference:

Cloned(Commentary)
Cloned (Commentary)
Organism
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
Homo sapiens
Engineering
Protein Variants
Commentary
Organism
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
Homo sapiens
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
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
mitochondrion
-
Homo sapiens
5739
-
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
Apocytochrome c + heme
Homo sapiens
-
Holocytochrome c
-
-
?
Organism
Organism
UniProt
Commentary
Textmining
Homo sapiens
P53701
-
-
Purification (Commentary)
Purification (Commentary)
Organism
recombinant GST-tagged enzyme and cytochrome c mutants from Escherichia coli strain RK103 membranes by ultracentrifugation, glutahione affinity chromatographyand ultrafiltration
Homo sapiens
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
Apocytochrome c + heme
-
730058
Homo sapiens
Holocytochrome c
-
-
-
?
Apocytochrome c + heme
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
730058
Homo sapiens
Holocytochrome c
-
-
-
?
Synonyms
Synonyms
Commentary
Organism
HCCS
-
Homo sapiens
holocytochrome c synthase
-
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
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
Homo sapiens
Engineering (protein specific)
Protein Variants
Commentary
Organism
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
Homo sapiens
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
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
mitochondrion
-
Homo sapiens
5739
-
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
Apocytochrome c + heme
Homo sapiens
-
Holocytochrome c
-
-
?
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant GST-tagged enzyme and cytochrome c mutants from Escherichia coli strain RK103 membranes by ultracentrifugation, glutahione affinity chromatographyand ultrafiltration
Homo sapiens
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
Apocytochrome c + heme
-
730058
Homo sapiens
Holocytochrome c
-
-
-
?
Apocytochrome c + heme
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
730058
Homo sapiens
Holocytochrome c
-
-
-
?
General Information
General Information
Commentary
Organism
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
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
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
Homo sapiens
Other publictions for EC 4.4.1.17
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
747125
Babbitt
Biosynthesis of single thioet ...
Homo sapiens
Biochemistry
56
3337-3346
2017
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749183
Mendez
Engineered holocytochrome c s ...
Homo sapiens
Proc. Natl. Acad. Sci. USA
114
2235-2240
2017
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748211
Babbitt
Molecular basis behind inabil ...
Homo sapiens
J. Biol. Chem.
291
17523-17534
2016
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1
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729264
Babbitt
Conserved residues of the huma ...
Homo sapiens
Biochemistry
53
5261-5271
2014
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12
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729740
Zhang
Substrate recognition of holoc ...
Saccharomyces cerevisiae
FEBS Lett.
588
3367-3374
2014
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11
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730058
Babbitt
Mechanisms of mitochondrial ho ...
Homo sapiens
J. Biol. Chem.
289
28795-18807
2014
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730827
San Francisco
Human mitochondrial holocytoch ...
Homo sapiens
Proc. Natl. Acad. Sci. USA
110
E788-E797
2013
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715034
Stevens
The mitochondrial cytochrome c ...
Saccharomyces cerevisiae
FEBS Lett.
585
1891-1896
2011
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729727
Moore
Mitochondrial cytochrome c syn ...
Saccharomyces cerevisiae
FEBS Lett.
585
3415-3419
2011
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730322
Kleingardner
Comparing substrate specificit ...
Saccharomyces cerevisiae
Metallomics
3
396-403
2011
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6
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2
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713714
Qidwai
Deletions of Xp provide eviden ...
Homo sapiens
Am. J. Med. Genet. A
152
1588-1590
2010
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715120
Corvest
c-type cytochrome assembly in ...
Saccharomyces cerevisiae
Genetics
186
561-571
2010
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691507
Kemmer
Combining chemical genomics sc ...
Saccharomyces cerevisiae
BMC Microbiol.
9
9-9
2009
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691983
Drenckhahn
Compensatory growth of healthy ...
Mus musculus
Dev. Cell
15
521-533
2008
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682001
Hartshorne
A dedicated haem lyase is requ ...
Wolinella succinogenes
Mol. Microbiol.
64
1049-1060
2007
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677440
Wimplinger
Mutations of the mitochondrial ...
Homo sapiens
Am. J. Hum. Genet.
79
878-889
2006
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679489
Kiryu-Seo
Unique anti-apoptotic activity ...
Mus musculus
EMBO J.
25
3411-3421
2006
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665678
Bernard
Cyc2p, a membrane-bound flavop ...
Saccharomyces cerevisiae
J. Biol. Chem.
280
39852-39859
2005
1
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652487
Bernard
Overlapping specificities of t ...
Homo sapiens, Mus musculus, Saccharomyces cerevisiae
J. Biol. Chem.
278
49732-49742
2003
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3
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6
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6
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652352
Ren
A bacterial cytochrome c heme ...
Escherichia coli
J. Biol. Chem.
277
7657-7663
2002
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651895
Tong
Cytochrome c heme lyase activi ...
Saccharomyces cerevisiae
J. Biol. Chem.
273
25695-25702
1998
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1
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