Information on EC 4.1.1.37 - uroporphyrinogen decarboxylase

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

EC NUMBER
COMMENTARY hide
4.1.1.37
-
RECOMMENDED NAME
GeneOntology No.
uroporphyrinogen decarboxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
uroporphyrinogen III = coproporphyrinogen III + 4 CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3,8-divinyl-chlorophyllide a biosynthesis I (aerobic, light-dependent)
-
-
3,8-divinyl-chlorophyllide a biosynthesis II (anaerobic)
-
-
3,8-divinyl-chlorophyllide a biosynthesis III (aerobic, light independent)
-
-
Biosynthesis of secondary metabolites
-
-
heme b biosynthesis I (aerobic)
-
-
heme b biosynthesis II (anaerobic)
-
-
heme b biosynthesis IV (Gram-positive bacteria)
-
-
Metabolic pathways
-
-
Porphyrin and chlorophyll metabolism
-
-
superpathway of heme b biosynthesis from uroporphyrinogen-III
-
-
heme metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
uroporphyrinogen-III carboxy-lyase (coproporphyrinogen-III-forming)
Acts on a number of porphyrinogens.
CAS REGISTRY NUMBER
COMMENTARY hide
9024-70-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Z strain
-
-
Manually annotated by BRENDA team
Z strain
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
intertidal grapsid crab
-
-
Manually annotated by BRENDA team
German backface sheep, mutation L131P is associated with a type pf porphyria
-
-
Manually annotated by BRENDA team
Wistar strain
-
-
Manually annotated by BRENDA team
strain PCC 7942
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-COOH-porphyrin I
?
show the reaction diagram
-
-
-
-
?
5-COOH-porphyrinogen I
Coproporphyrinogen I + CO2
show the reaction diagram
5-COOH-porphyrinogen III
Coproporphyrinogen III + CO2
show the reaction diagram
6-COOH-porphyrinogen I
Coproporphyrinogen I + CO2
show the reaction diagram
6-COOH-porphyrinogen III
Coproporphyrinogen III + CO2
show the reaction diagram
7-COOH-porphyrinogen
Coproporphyrinogen + CO2
show the reaction diagram
-
-
-
-
-
7-COOH-porphyrinogen I
Coproporphyrinogen I + CO2
show the reaction diagram
7-COOH-porphyrinogen III
Coproporphyrinogen III + CO2
show the reaction diagram
8-carboxylporphyrinogen
coproporphyrinogen(4-COOH) + CO2
show the reaction diagram
8-COOH-porphyrinogen
Coproporphyrinogen + CO2
show the reaction diagram
-
-
-
-
-
8-COOH-porphyrinogen I
Coproporphyrinogen I + CO2
show the reaction diagram
-
-
-
-
-
8-COOH-porphyrinogen III
Coproporphyrinogen III + CO2
show the reaction diagram
-
-
-
-
-
heptaporphyrinogen III
hexaporphyrinogen III + CO2
show the reaction diagram
-
-
-
-
?
hexaporphyrinogen III
pentaporphyrinogen III + CO2
show the reaction diagram
-
-
-
-
?
pentacarboxylic porphyrinogen I
coproporphyrinogen-I + 4 CO2
show the reaction diagram
-
-
-
-
?
Uroporphyrinogen
Coproporphyrinogen + CO2
show the reaction diagram
-
-
-
-
-
uroporphyrinogen I
coproporphyrinogen I + 4 CO2
show the reaction diagram
uroporphyrinogen I
pentaporphyrinogen I + CO2
show the reaction diagram
-
-
-
-
?
uroporphyrinogen III
coproporphyrinogen + CO2
show the reaction diagram
Uroporphyrinogen III
Coproporphyrinogen III + CO2
show the reaction diagram
uroporphyrinogen-I
coproporphyrinogen-I + 4 CO2
show the reaction diagram
-
-
-
-
?
uroporphyrinogen-III
coproporphyrinogen-III + 4 CO2
show the reaction diagram
uroporphyrinogen-III
coproporphyrinogen-III + CO2
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
uroporphyrinogen III
coproporphyrinogen + CO2
show the reaction diagram
Uroporphyrinogen III
Coproporphyrinogen III + CO2
show the reaction diagram
uroporphyrinogen-III
coproporphyrinogen-III + 4 CO2
show the reaction diagram
-
-
-
-
?
uroporphyrinogen-III
coproporphyrinogen-III + CO2
show the reaction diagram
-
first branching point of the ubiquitous tetrapyrrole biosynthetic pathway, chlorophyll and heme biosynthesis
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
-
slight activation
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,2'-dipyridyl disulfide
-
-
2,3,2',3'-Tetrachlorobiphenyl
-
-
2,3,4,2',3',4'-Hexachlorobiphenyl
-
-
2,4,2',4'-Tetrachlorobiphenyl
-
-
2,4,5,3',4'-Pentabromobiphenyl
-
-
2,4,6,2',4',6'-Hexachlorobiphenyl
-
-
2,5,2',5'-Tetrachlorobiphenyl
-
-
2,6,2',6'-Tetrachlorobiphenyl
-
-
2-mercaptoethanol
-
-
3,4,3',4'-Tetrachlorobiphenyl
-
-
3,4,5,3',4',5'-Hexachlorobiphenyl
-
-
3,5,3',5'-Tetrachlorobiphenyl
-
-
5,5'-dithiobis(2-nitrobenzoate)
7-COOH-porphyrin III
-
most effective inhibitor of decarboxylation of both uroporphyrinogen III and 7-COOH-porphyrinogen III
7-COOH-porphyrinogen I
-
inhibits decarboxylation of 7-COOH-porphyrinogen III
7-COOH-porphyrinogen III
-
inhibits decarboxylation of 7-COOH-porphyrinogen I
acetone
-
-
Al3+
-
-
arachidonate
-
-
Butanedione
-
-
Co2+
-
-
Coproporphyrin I
-
-
coproporphyrin III
-
-
diethyldicarbonate
ethanol
-
-
Haematoporphyrin IX
-
-
hexachlorobenzene treatment generated inhibitor
-
-
-
HtpG
-
suppresses HemE activity at 0.25 nmol or 1.25 nmol
-
iodoacetamide
iodoacetate
-
-
Isopropyl alcohol
-
-
linolate
-
-
mesoporphyrin IX
-
-
methanol
-
-
Mn2+
-
strong
NaCl
-
-
Nonporphyrin products
-
-
-
O2
-
autooxidation of uroporphyrinogen
oleate
-
-
p-hydroxymercuribenzoate
-
-
Phenylglyoxal
PI-16
-
-
porphomethene
protoporphyrin IX
-
-
Sn2+
-
weak
uroporphyrin III
-
-
Uroporphyrinogen I
uroporphyrinogen III
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta-mercaptoethanol
-
absolute requirement for activity
dithiothreitol
EDTA
-
enhances activity
reduced glutathione
-
enhances activity
Reducing agents
-
required
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.8 - 4.2
5-COOH-porphyrin I
-
0.00007 - 0.00215
5-COOH-porphyrinogen I
0.00005 - 0.00043
5-COOH-porphyrinogen III
0.0003 - 0.00285
6-COOH-porphyrinogen I
0.00064
6-COOH-porphyrinogen III
-
-
0.00231
7-COOH, porphyrinogen
-
isoenzyme UROD54000
0.000231 - 0.0013
7-COOH-porphyrinogen
0.000007 - 0.00085
7-COOH-porphyrinogen I
0.00035
7-COOH-porphyrinogen III
-
-
0.0015 - 0.0105
8-carboxylporphyrinogen
0.00079
8-COOH-porphyrinogen I
-
-
0.00025 - 0.00053
8-COOH-porphyrinogen III
0.003 - 0.005
uroporphyrinogen
-
-
-
0.00001 - 0.0109
Uroporphyrinogen I
0.000006 - 0.0087
uroporphyrinogen III
0.0277 - 0.0381
uroporphyrinogen-I
0.0108 - 0.0148
uroporphyrinogen-III
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.102 - 0.124
uroporphyrinogen-I
0.317 - 0.425
uroporphyrinogen-III
additional information
additional information
Rhodopseudomonas palustris
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0099
PI-16
Homo sapiens
-
in 0.1 M Tris, pH 7.7, 7.5 mM dithiothreitol, at 37C`
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0013
-
-
0.0018
-
-
0.0035
-
-
0.016
-
-
0.0237
-
-
0.0583
-
-
0.17
-
-
0.75
-
crude enzyme, at 37C
7.6
-
purified enzyme, at 37C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.7
-
uroporphyrinogen I, uroporphyrinogen III or 7-COOH-porphyrinogen I, estimation by coproporphyrinogen formation
7.6
-
partial reactions: synthesis of 6-COOH porphyrinogen and 5-COOH porphyrinogen from uroporphyrinogen I
additional information
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 6.6
-
pH 5.0: about 80% of maximal activity, pH 6.6: about 40% of maximal activity, 5-COOH-porphyrinogen I
5 - 8
-
in 0.2 M KH2PO4, 0.1 mM dithiothreitol
5.3 - 8
-
pH 5.3: about 60% of maximal activity, pH 8.0: about 65% of maximal activity
5.8 - 7.4
-
pH 5.8: about 65% of maximal activity, pH 7.4: about 45% of maximal activity, uroporphyrinogen I
5.8 - 7.8
-
pH 5.8: about 60% of maximal activity, pH 7.8: about 55% of maximal activity, 5-COOH-porphyrinogen III
6 - 7.4
-
pH 6.0: about 55% of maximal activity, pH 7.4: about 50% of maximal activity, uroporphyrinogen III
6 - 7.2
-
pH 6.0: about 50% of maximal activity, pH 7.2: about 60% of maximal activity, uroporphyrinogen III
6.1 - 7.9
-
-
6.2 - 7.7
-
pH 6.2: about 25% of maximal activity, pH 7.7: about 70% of maximal activity
6.4 - 7.9
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
recombinant enzyme
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 70
28 - 74
-
activity increases up to 50C and decreases sharply at 74C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.4
-
calculated from amino acid sequence
9.4
-
calculated isoelectric point
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Aquifex aeolicus (strain VF5)
Bacillus subtilis (strain 168)
Burkholderia thailandensis (strain ATCC 700388 / DSM 13276 / CIP 106301 / E264)
Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34000
-
isoenzyme II, gel filtration
38000 - 39000
-
gel filtration, nondenaturing PAGE
38000
-
1 * 38000, SDS-PAGE
39000
-
2 * 39000, SDS-PAGE
39500
-
x * 39500, SDS-PAGE
39700
-
2 * 39700, SDS-PAGE
40500
-
2 * 40500, dynamic light scattering
40831
-
x * 40831, calculation from nucleotide sequence
41070
-
calculated from amino acid sequence; mass spectrometry
43000
-
SDS-PAGE
44000
-
x * 44000, uroporphyrinogen decarboxylase containing a histidine tag on the amino terminal end, SDS-PAGE
48000
-
gel filtration
52000 - 54000
-
isoenzyme I, gel filtration
52000
-
1 * 52000, isoenzyme I, SDS-PAGE
58000
-
gel filtration
60000
-
SDS-PAGE, monomer
64000
-
SDS-PAGE
65000
-
Western blot
66000
-
uroporphyrinogen decarboxylase containing a histidine tag on the amino terminal end, gel filtration
79000
-
gel filtration
80000
-
SDS-PAGE
81000
-
dynamic light scattering
82000
-
sedimentation equilibrium
83590
-
calculated from His-tagged amino acid sequence
84000
-
SDS-PAGE scURO-D-protein
86000
-
analytical ultracentrifugation scURO-D
90000
-
SDS-PAGE, active dimeric form
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
monomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glutathionylation
Cys52 of the enzyme can be glutathionylated and subsequently deglutathionylated by Grx2p in vitro
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapour diffusion with 25% polyethylene glycol-monomethyl ether 2000 and 160 mM sodium acetate in 100 mM citrate, pH 5.6, at 20C
-
crystallized in complex with coproporphyrinogen by sitting drop vapor diffusion, crystals belong to space group P3(1)21, unit cell dimensions a : b :102.9 A, c : 74.5 A
-
modified enzyme single-chain URO-D crystals are isomorphous with wild-type uroporphyrinogen decarboxylase crystals
-
mutant URO-D proteins G156D, F232L, and I260T
-
recombinant mutant proteins K297N and G318R
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hanging drop vapor diffusion method, space group P622,unit cell constants a : b : 158.44 A, c : 67.68 A
-
hexagonal space group P622, unit cell parameters a : b : 158.44 A, c : 67.68 A
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
-
unstable below
4445
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 60
-
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
4-porphyrinogen protects the enzyme from inhibitor action
-
recombinant enzymes are catalytically less efficient compared with the host enzyme
-
unstable in absence of 2-mercaptoethanol
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
rapid inactivation by uroporphyrin-catalyzed photooxidation
-
4440
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, stable for 3 months
-
-20C or 4C, 50 mM sodium phosphate buffer, pH 7.5, containing 300 mM imidazole, 1% Triton X-100, 50 mM NaCl, and 10% glycerol, more than a week, significant loss in activity
-
-20C, in 30-70% ammonium saturation fraction, 2 weeks, remains stable
-
-20C, in 30-70% ammonium saturation fraction, 8 weeks, 50% loss of activity
-
-20C, stable for at least 2 months, partially purified enzyme
-
-20C, stable for several months
-
-20C, unprecipitated protein, 2 weeks, 36% loss of activity
-
-70C, stable
-
frozen in 25 mM potassium phosphate buffer, pH 7.0, containing 2-mercaptoethanol, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
IMAC column chromatography, Mono Q column chromatography, and Superdex 70 gel filtration
-
isoenzymes I and II
-
mutant URO-D proteins G156D, F232L, and I260T
-
Ni-nitriloacetic acid column chromatography
-
Ni-NTA column
-
Ni-NTA column chromatography
Ni-NTA column chromatography and gel filtration
-
partial, Superdex 75 gel filtration
-
substrate ligand column is developed by covalently linking coproporphyrin-III to a Sepharose resin. The ligand-resin chromatography step rapidly separates coproporphyrinogen oxidase from uroporphyrinogen decarboxylase
-
wild-type and mutant enzymes
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned, sequenced and expressed in Escherichia coli
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21-pLysS
-
expressed in Escherichia coli BL21-RIL(DE3) cells
-
expressed in Escherichia coli Rosetta2 cells
-
expressed in Escherichia coli strain Top10
-
expression in Escherichia coli
-
expression in Escherichia coli as His-tagged enzyme
-
native enzyme and N-terminally truncated UROD are expressed in Escherichia coli Rosetta2(DE3)pLysS cells
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overexpression in Escherichia coli
-
partial cDNA clone
-
uroporphyrinogen decarboxylase mutations G318R, D306Y and K297N
-
wild-type enzyme and mutants causing porphyria cutanea tarda, expression in Escherichia coli BL-21
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
UROD is significantly overexpressed in head and neck cancer patient biopsies
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A22V
-
soluble but reduced catalytic activity
A80S
-
less than 12% of the specific activity of wild-type enzyme, Q38R-glutathione S-transferase fusion protein
C705A
-
site-directed mutagenesis
D306Y
-
mutation results in an insoluble recombinant protein
D79N
-
misfolded protein that is trafficked to inclusion bodies
D86
-
site-directed mutagenesis
D86E
-
site-directed mutagenesis
D86G
-
site-directed mutagenesis
F217Y
-
recombinant mutant of the single chain of both modules substrate uroporphyrinogen-I, 2.5% of recombinant wild-type; recombinant mutant of the single chain of both modules substrate uroporphyrinogen-III, 14.5% of recombinant wild-type; recombinant mutant of the single chain of the first module substrate uroporphyrinogen-I, 41.3% of recombinant wild-type; recombinant mutant of the single chain of the first module substrate uroporphyrinogen-II, 50.9% of recombinant wild-type; recombinant mutant of the single chain of the second module substrate uroporphyrinogen-I, 46.2% of recombinant wild-type; recombinant mutant of the single chain of the second module substrate uroporphyrinogen-III, 52.7% of recombinant wild-type; recombinant mutant substrate uroporphyrinogen-I, 2.6% of recombinant wild-type
F229L
-
site-directed mutagenesis
F84I
-
soluble but reduced catalytic activity
G170D
-
the missense mutation is associated with hepatoerythropoietic porphyria and shows erythrocyte UROD activity of 42% of normal. The recombinant UROD protein shows a relative activity of 17% and 60% of wild type to uroporphyrinogen I and III respectively
G281E
-
the mutation is associated with hepatoerythropoietic porphyria
G318R
-
little effect on the structure or activity of recombinant uroporphyrinogen decarboxylase, but the protein displays reduced stability in vitro
K297N
-
little effect on the structure or activity of recombinant uroporphyrinogen decarboxylase, but the protein displays reduced stability in vitro
M01T
-
site-directed mutagenesis
M1I
-
the absence of an initial methionine codon within the messenger RNA (mRNA) Kozac consensus sequence is predicted to lead to a loss of translation from the mutant allele
M1V/P235S
-
the mutation is associated with UROD deficiency
M324T
-
site-directed mutagenesis
P150L
-
misfolded protein that is trafficked to inclusion bodies
Q116X
-
this may yield a truncated protein of 115 amino acids or nonsense-mediated mRNA decay
Q206X
-
inactive mutant, Q38R-glutathione S-transferase fusion protein
Q38R
-
less than 0.2% of the specific activity of wild-type enzyme, Q38R-glutathione S-transferase fusion protein
T141I
-
soluble but reduced catalytic activity
T160I
-
3.4% of the specific activity of wild-type enzyme, Q38R-glutathione S-transferase fusion protein
T20C
-
site-directed mutagenesis
T989C
-
site-directed mutagenesis
Y164F
-
site-directed mutagenesis
Y164G
-
recombinant mutant of the single chain of the first module substrate uroporphyrinogen-I, 13.2% of recombinant wild-type; recombinant mutant substrate uroporphyrinogen-I, 8.1% of recombinant wild-type
Y182C
-
soluble but reduced catalytic activity
K150T
-
the mutation does not have a significant effect on Vmax, but decreases Km by 25%
K150T/K219E
-
the Km of the double mutant decreases by around 40%
K150T/K219E/K277P
-
the mutant shows no significant change in Km, but the Vmax increases by 3.7fold
K277P
-
the mutant decreases Km by 40%
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
agriculture
diagnostics
-
uroporphyrinogen decarboxylase activity has a high diagnostic accuracy for differentiating the 2 Porphyria cutanea tarda types, the sporadic (sPCT) and familial (fPCT) forms, which are generally clinically indistinguishable, a model that takes into account both clinical information and laboratory test results can be used to predict fPCT
medicine
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