Information on EC 4.99.1.1 - ferrochelatase

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

EC NUMBER
COMMENTARY hide
4.99.1.1
-
RECOMMENDED NAME
GeneOntology No.
ferrochelatase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protoheme + 2 H+ = protoporphyrin + Fe2+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
heme biosynthesis I (aerobic)
-
-
heme biosynthesis II (anaerobic)
-
-
heme metabolism
-
-
Metabolic pathways
-
-
Porphyrin and chlorophyll metabolism
-
-
superpathway of heme biosynthesis from uroporphyrinogen-III
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-
SYSTEMATIC NAME
IUBMB Comments
protoheme ferro-lyase (protoporphyrin-forming)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9012-93-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
chironomid larvae
SwissProt
Manually annotated by BRENDA team
strain CC124
SwissProt
Manually annotated by BRENDA team
strain CC124
SwissProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
zebrafish
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
var. PI 177418
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Rhizopus oryzae RA 99-880
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
-
siRNA-mediated knockdown of ferrochelatase suppresses heme synthesis and significantly increases intracellular protoporphyrin IX (PpIX) accumulation, this improves the phototoxicity of 5-aminolevulinic acid-based photodynamic therapy in urothelial cancer cell lines
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,4-disulfonic deuteroporphyrin + Fe2+
?
show the reaction diagram
-
-
-
?
Cd2+-protoporphyrin + H+
protoporphyrin + Cd2+
show the reaction diagram
-
poor substrate
-
-
?
Co2+-protoporphyrin + H+
protoporphyrin + Co2+
show the reaction diagram
-
-
-
-
?
deuteroporphyrin + Fe2+
deuteroheme + H+
show the reaction diagram
deuteroporphyrin + Fe2+
protoheme + H+
show the reaction diagram
-
-
-
-
-
deuteroporphyrin + Mn2+
? + H+
show the reaction diagram
-
in contrast to protoporphyrin IX, deuteroporphyrin lacks the vinyl groups at the 2- and 4-ring positions, and therefore, it is possible to structurally discriminate enzyme-bound (metallated) deuteroporphyrin from any possible heme (protoheme) carryover from the enzyme preparation
-
-
?
deuteroporphyrin + Ni2+
? + H+
show the reaction diagram
-
the Ni-deuteroporphyrin structure is distinctly different from the Mn-deuteroporphyrin model, despite the only variation in enzyme preparation being the addition of either Ni or Mn
-
-
?
deuteroporphyrin IX + Zn2+
Zn deuteroporphyrin IX + H+
show the reaction diagram
-
in vitro, zinc is the preferred substrate at all concentrations of porphyrin
-
-
?
deuteroporphyrin IX + Zn2+
Zn-deuteroporphyrin IX + H+
show the reaction diagram
Fe2+-2,4-bis-acetal deuteroporphyrin
?
show the reaction diagram
-
-
-
-
?
Fe2+-2,4-diacetyldeuteroporphyrin
?
show the reaction diagram
-
-
-
-
?
Fe2+-2,4-disulfonate deuteroporphyrin
?
show the reaction diagram
-
-
-
-
?
Fe2+-hematoporphyrin
?
show the reaction diagram
Fe2+-mesoporphyrin IX + H+
mesoporphyrin IX + Fe2+
show the reaction diagram
-
-
-
-
?
Fe2+-protoporphyrin + H+
protoporphyrin + Fe2+
show the reaction diagram
-
-
-
-
?
heme + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
-
-
-
-
?
hemin + H+
mesoporphyrin IX + Zn2+
show the reaction diagram
-
-
-
-
r
hemoglobin + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
mesoporphyrin + Fe2+
mesoheme
show the reaction diagram
pH 8.0
-
-
?
mesoporphyrin + Fe2+
mesoheme + H+
show the reaction diagram
mesoporphyrin + Zn2+
mesoheme
show the reaction diagram
-
37C
-
-
?
mesoporphyrin + Zn2+
Zn-mesoporphyrin + H+
show the reaction diagram
-
-
-
-
?
mesoporphyrin IX + Fe2+
?
show the reaction diagram
mesoporphyrin IX + Fe2+
mesoheme IX + H+
show the reaction diagram
mesoporphyrin IX + Fe2+
protoporphyrin IX + H+
show the reaction diagram
-
-
-
-
?
mesoporphyrin IX + ferrous ammonium sulfate
mesoheme + ammonium sulfate
show the reaction diagram
-
room temperature
-
-
?
mesoporphyrin IX + Zn2+
hemin + H+
show the reaction diagram
-
-
-
-
r
myoglobin + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
N-methyl mesoporphyrin + Cu2+
?
show the reaction diagram
-
pH 7.4
-
-
?
N-methyl mesoporphyrin + Zn2+
?
show the reaction diagram
-
pH 7.4
-
-
?
porphyrin + Fe2+
heme + H+
show the reaction diagram
-
-
-
-
?
porphyrin + metal ion
metalloporphyrin
show the reaction diagram
protoheme + H+
protoporphyrin + Fe2+
show the reaction diagram
protoporphyrin + Cu2+
Cu2+-protoporphyrin + H+
show the reaction diagram
-
-
-
?
protoporphyrin + Fe2+
protoheme + 2 H+
show the reaction diagram
protoporphyrin + Fe2+
protoheme + H+
show the reaction diagram
protoporphyrin + Zn2+
Zn2+-protoporphyrin + H+
show the reaction diagram
protoporphyrin IX + Co2+
Co2+-protoporphyrin + H+
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Cu2+
Cu2+-protoporphyrin + H+
show the reaction diagram
-
Cu2+ is a good substrate
-
-
?
protoporphyrin IX + Fe2+
?
show the reaction diagram
protoporphyrin IX + Fe2+
heme + H+
show the reaction diagram
-
-
-
?
protoporphyrin IX + Fe2+
protoheme + H+
show the reaction diagram
protoporphyrin IX + Fe2+
protoheme IX + H+
show the reaction diagram
protoporphyrin IX + FeCl3
protoheme + HCl
show the reaction diagram
pH 7.5, 37C
-
-
-
protoporphyrin IX + Ni2+
?
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Zn2+
?
show the reaction diagram
-
-
-
?
protoporphyrin IX + Zn2+
Zn protoporphyrin IX
show the reaction diagram
-
pH 7.4, room temperature
-
-
?
protoporphyrin IX + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Zn2+
Zn-protoporphyrin IX
show the reaction diagram
protoporphyrin IX + Zn2+
Zn-protoporphyrin IX + H+
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Zn2+
Zn2+-protoporphyrin IX + H+
show the reaction diagram
-
-
-
-
?
Sn2+-protoporphyrin + H+
protoporphyrin + Sn2+
show the reaction diagram
-
-
-
-
?
Zn2+-mesoporphyrin + H+
mesoporphyrin + Zn2+
show the reaction diagram
Zn2+-protoporphyrin + H+
protoporphyrin + Zn2+
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
protoheme + H+
protoporphyrin + Fe2+
show the reaction diagram
protoporphyrin + Fe2+
protoheme + 2 H+
show the reaction diagram
protoporphyrin + Fe2+
protoheme + H+
show the reaction diagram
protoporphyrin IX + Fe2+
?
show the reaction diagram
protoporphyrin IX + Fe2+
protoheme IX + H+
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
heme
-
-
[2Fe-2S]-center
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
absolute requirement
Hg2+
-
human ferrochelatase is capable of catalyzing the insertion of the inhibitory metal ion Hg2+ into a porphyrin macrocycle
Pb2+
0.1 mM, reduces the enzymatic activity by more than 60%
Sn2+
-
-
[2Fe-2S]cluster
additional information
-
no [2Fe-2S] cluster
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,2'-dipyridyl
-
-
deferoxamine
-
-
deuteroporphyrin IX
-
-
Divalent cations
-
-
-
Fe2+
-
Zn2+-chelatase activity
iodacetic acid
-
-
iodoacetamide
metalloporphyrin
-
containing Fe2+, Co2+, Zn2+, Sn2+
-
Metalloporphyrins
-
-
-
Mg2+
0.1 mM, reduces the enzymatic activity by more than 60%
Mg2+-protoporphyrin
-
-
monobromobimane
-
-
N-alkylated porphyrins
N-ethylmaleimide
N-methyl mesoporphyrin
-
transition-state inhibitor
N-methylmesoporphyrin
N-Methylprotoporphyrin
N-methylprotoporphyrin IX
-
Ni2+
-
substrate inhibition occurs when assayed in the absence of metal ion-complexing buffer components
p-chloromercuribenzoate
-
-
porphyrin
-
high porphyrin concentrations noticeably increase the extent of zinc inhibition
porphyrin isomer
-
competitive
-
Porphyrins
protohaem
-
-
-
sulfhydryl reagents
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
Cu2+
0.1 mM, causes 4fold increase in activity
L-cysteine
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.056
2,4-bisacetal deuteroporphyrin
-
-
-
0.479
2,4-diacetyldeuteroporphyrin
-
-
-
0.052
2,4-disulfonic deuteroporphyrin
-
-
-
0.0052 - 0.56
Co2+
0.063 - 0.17
Cu2+
0.0213
deuteroporphyrin
-
-
0.0026 - 0.0461
deuteroporphyrin IX
0.00048 - 0.166
Fe2+
0.055
hematoporphyrin
-
-
0.0057
Hemin
-
pH 5.5, 45C
0.004 - 0.1
mesoporphyrin
0.0047 - 0.0302
mesoporphyrin IX
0.012
Myoglobin
-
at pH 6.5 and 30C
-
0.02206 - 0.1037
Ni2+
0.0121 - 0.0246
porphyrin
0.002 - 0.05
protoporphyrin
0.00022 - 0.116
protoporphyrin IX
0.00017 - 0.06
Zn2+
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.016 - 0.033
Co2+
0.065
Cu2+
Bacillus subtilis
-
wild type enzyme, in 100 mM tris(hydroxymethyl)aminomethane-HCl, pH 7.4, temperature not specified in the publication
0.018 - 0.3
Fe2+
0.52
Hemin
Sus scrofa
-
pH 5.5, 45C
6.7
mesoporphyrin IX
Sus scrofa
-
pH 8.0, 37C
0.01167 - 0.0573
porphyrin
0.3 - 0.483
protoporphyrin
Bacillus subtilis
-
-
0.0125 - 1.9
protoporphyrin IX
0.034 - 6.7
Zn2+
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
76 - 1200
deuteroporphyrin IX
62.5 - 416.8
Fe2+
0.000092
Hemin
Sus scrofa
-
pH 5.5, 45C
822
0.00101
mesoporphyrin IX
Sus scrofa
-
pH 8.0, 37C
2159
0.56 - 9.05
Ni2+
47.3 - 2015
protoporphyrin IX
0.00525 - 19000
Zn2+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0712 - 0.3376
deuteroporphyrin IX
0.0014 - 0.00251
N-Methylprotoporphyrin
0.007 - 2.4
Ni2+
additional information
additional information
-
Ki-values of porphyrin isomers that are not substrates are in the range of 0.013-0.07 mM, Ki-values of metalloporphyrin isomers that are not substrates are in the range of 0.002-0.013 mM, Ki-values for metal inhibitors are in the range of 0.01-0.05 mM
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0015
-
at pH and C
0.033
-
R31G, pH 7.6, 30C, unaerobic conditions
0.041
-
wild-type, pH 7.6, 30C, unaerobic conditions
0.054
-
mutant T302A, pH 7.6, 30C, unaerobic conditions
0.056
-
mutant D76G/K102T, pH 7.6, 30C, unaerobic conditions
0.065
-
M11V/G104A, pH 7.6, 30C, unaerobic conditions
0.067
-
mutant E61K, pH 7.6, 30C, unaerobic conditions
0.093
-
E61K/L185Q/G212D, pH 7.6, 30C, unaerobic conditions
0.413
-
-
15.2
-
pH 8.0, 37C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 6
-
-
5.5
-
reverse reaction
5.5 - 6
-
pH optimum for zinc removal
7.3
-
etioplast
7.3 - 7.5
-
2 optima, pH 7.3-7.5, pH 8.0-8.2, deuteroheme formation
7.5 - 8
8 - 8.2
-
2 optima, pH 7.3-7.5, pH 8.0-8.2, deuteroheme formation
8.25
-
protoporphyrin
8.35
-
mesoporphyrin
8.45
-
deuteroporphyrin
additional information
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3 - 8.6
-
-
6.8 - 8.3
-
-
6.8 - 9.5
-
-
7.2 - 8.8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18 - 37
-
Q10: 2.9 kcal/mol
55.8
-
Tm, wild-type in phosphate buffer
56
-
Tm, wild-type in bicine buffer
57.5
-
Tm, mutant E289A
61
-
Tm, mutant E289Q
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.12
predicted from amino acid sequence
7.35
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
conversion of mesoporphyrin is dependent on the expression of ferrochelatase, since control Balb/3T3 cells have much lower expression of ferrochelatase than the ferrochelatase transfectants
Manually annotated by BRENDA team
-
splenic erythroblast
Manually annotated by BRENDA team
-
cultured
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the recombinant protein expressed in Escherichia coli
Manually annotated by BRENDA team
-
preprotein with a cleavable presequence at its amino-terminus
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
ORGANISM
UNIPROT
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)
Bacillus subtilis (strain 168)