Information on EC 1.3.98.3 - coproporphyrinogen dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.3.98.3
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RECOMMENDED NAME
GeneOntology No.
coproporphyrinogen dehydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
coproporphyrinogen III + 2 S-adenosyl-L-methionine = protoporphyrinogen IX + 2 CO2 + 2 L-methionine + 2 5'-deoxyadenosine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
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oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3,8-divinyl-chlorophyllide a biosynthesis II (anaerobic)
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Biosynthesis of secondary metabolites
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heme b biosynthesis II (anaerobic)
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Metabolic pathways
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Porphyrin and chlorophyll metabolism
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heme metabolism
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SYSTEMATIC NAME
IUBMB Comments
coproporphyrinogen-III:S-adenosyl-L-methionine oxidoreductase (decarboxylating)
This enzyme differs from EC 1.3.3.3, coproporphyrinogen oxidase, by using S-adenosyl-L-methionine (AdoMet) instead of oxygen as oxidant. It occurs mainly in bacteria, whereas eukaryotes use the oxygen-dependent oxidase. The reaction starts by using an electron from the reduced form of the enzyme's [4Fe-4S] cluster to split AdoMet into methionine and the radical 5'-deoxyadenosin-5'-yl. This radical initiates attack on the 2-carboxyethyl groups, leading to their conversion into vinyl groups. This conversion, ---(.)CH-CH2-COO- -> ---CH=CH2 + CO2 + e- replaces the electron initially used.
CAS REGISTRY NUMBER
COMMENTARY hide
9076-84-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
gene hemW or hemN
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Manually annotated by BRENDA team
gene hemN
UniProt
Manually annotated by BRENDA team
two hemN genes, sll1876 and sll1917
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-
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
oxidized coproporphyrinogen III accumulates in a hemN2- mutant in Rubrivirax gelatinosus only under oxygen limited conditions
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-deoxy-scyllo-inosamine + S-adenosyl-L-methionine
3-amino-2,3-dideoxy-scyllo-inosose + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
2-deoxystreptamine + S-adenosyl-L-methionine
? + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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14.4% activity compared to 2-deoxy-scyllo-inosamine
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-
?
coproporphyrinogen III + 2 S-adenosyl-L-methionine
protoporphyrinogen IX + 2 CO2 + 2 L-methionine + 2 5'-deoxyadenosine
show the reaction diagram
coproporphyrinogen III + S-adenosyl-L-methionine
protoporphyrinogen IX + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
coproporphyrinogen-III + S-adenosyl-L-methionine
protoporphyrinogen IX + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
harderoporphyrinogen + 2 S-adenosyl-L-methionine
protoporphyrinogen IX + 2 CO2 + 2 L-methionine + 2 5'-deoxyadenosine
show the reaction diagram
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HemN can utilize chemically synthesized harderoporphyrinogen as a substrate and converts it to protoporphyrinogen IX
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?
harderoporphyrinogen + S-adenosyl-L-methionine
protoporphyrinogen IX + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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chemical substrate sythesis, overview
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?
myo-inositol + S-adenosyl-L-methionine
? + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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0.9% activity compared to 2-deoxy-scyllo-inosamine
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-
?
scyllo-inositol + S-adenosyl-L-methionine
? + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
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3.3% activity compared to 2-deoxy-scyllo-inosamine
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?
additional information
?
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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
coproporphyrinogen III + 2 S-adenosyl-L-methionine
protoporphyrinogen IX + 2 CO2 + 2 L-methionine + 2 5'-deoxyadenosine
show the reaction diagram
coproporphyrinogen III + S-adenosyl-L-methionine
protoporphyrinogen IX + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
coproporphyrinogen-III + S-adenosyl-L-methionine
protoporphyrinogen IX + CO2 + L-methionine + 5'-deoxyadenosine
show the reaction diagram
additional information
?
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HemW shows no coproporphyrinogen III oxidase activity in vivo or in vitro
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4Fe-4S-center
iron-sulfur centre
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in Sll1876 and Sll1917
NADPH
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requires NAD(P)H, lower activity than with NADH as cofactor
S-adenosyl-L-methionine
[3Fe-4S]1+ cluster
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[4Fe-4S]-center
[4Fe-4S]1+ cluster
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe
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contains 4 irons per polypeptide
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-deoxy-scyllo-inosamine
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uncompetitive substrate inhibition
Cu2+
Cu2+ affects tetrapyrrole biosynthesis presumably at the level of the S-adenosyl-L-methionine and [4Fe-4S] containing HemN enzyme, copper targets the 4Fe-4S clusters in the anaerobic enzyme
EDTA
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strong inhibition
H2O2
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enzyme inactivation at 30%
o-phenanthroline
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strong inhibition
O2
O2 affects tetrapyrrole biosynthesis presumably at the level of the S-adenosyl-L-methionine and [4Fe-4S] containing HemN enzyme
additional information
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not inhibited by S-adenosyl-L-methionine
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
DTT
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added to the assay at 2 mM
NADH
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added to the assay at 0.5 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.022
2-deoxy-scyllo-inosamine
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in 50 mM HEPES-NaOH (pH 8.0) in the presence of 10 mM sodium dithionite at 28°C
0.0052 - 0.0067
Coproporphyrinogen III
0.15 - 0.46
S-adenosyl-L-methionine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.038
2-deoxy-scyllo-inosamine
Bacillus circulans
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in 50 mM HEPES-NaOH (pH 8.0) in the presence of 10 mM sodium dithionite at 28°C
360 - 900
Coproporphyrinogen III
0.02 - 0.022
S-adenosyl-L-methionine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
54000 - 175000
Coproporphyrinogen III
4234
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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in vivo, HemW occurs as a heme-free cytosolic form, as well as a heme-containing membrane-associated form
Manually annotated by BRENDA team
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in vivo, HemW occurs as a heme-free cytosolic form, as well as a heme-containing membrane-associated form
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52000
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gel filtration in combination with glycerol gradient centrifugation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
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structure analysis of recombinant His-tagged viperin (214-361) by UV-visible, circular dichroism, and NMR spectroscopy, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure
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crystal structure, co-crystallized with S-adenosyl-L-methionine, hanging-drop vapor diffusion method, X-ray analysis
presence of an unusually coordinated iron-sulfur cluster and two molecules of S-adenosylmethionine, which is of functional importance
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under strictly anaerobic conditions, comparison of the crystal structures of the three radical SAM enzymes HemN, BioB and MoaA show that the enzymes are structurally significantly different
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by a single chromatographic step under anaerobic conditions
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by affinity chromatography
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His-bind resin column chromatography
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recombinant GST-tagged enzyme by glutathione affinity chromatography and ultrafiltration; recombinant HemN from Escherichia coli strain BL21(DE3)
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recombinant HemN
recombinant His-tagged full-length enzyme and viperin (214-361) from Escherichia coli strain BL21 inclusion bodies, solubilization by 8 M urea and purification by nickel affinity chromatography and gel filtration
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recombinant His-tagged HemN from Escherichia coli strain BL21(DE3) membranes by nickel affinity chromatography and gel filtration
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recombinant terminally Strep-tagged HemNs from Escherichia coli to homogeneity
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recombinant wild-type and mutant HemN
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Strep-Tactin-Sepharose column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
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expressed in Escherichia coli BL21 cells
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expressed in Escherichia coli strain BL21(DE3)
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gene cig5, expression of viperin lacking the leucine zipper domain, viperin43-340, in Escherichia coli Rosetta(DE3)pLysS cells
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gene hemN, expression in Escherichia coli strain BL21(DE3); recombinant expression as GST-fusion protein
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gene hemW or hemN, recombinant expression in the hemN-deficient Escherichia coli mutant strain JW3838 and in strain BL21(DE3) as His-tagged protein. Lactococcus lactis HemW at high levels does not complement the growth deficit of the Escherichia coli DELTAhemN mutant
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genes sll1876 and sll1917, overexpression of N-terminally Strep-tagged HemNs in Escherichia coli
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hemeN gene, overexpression in Escherichia coli BL21(DE3)
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mutated enzymes expressed in Escherichia coli BL21(DE3)
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viperin from monocytic cells, DNA and amino acid sequence determination and analysis, expression of His-tagged full-length enzyme, and of His-tagged viperin (45-361) and viperin (214-361) in Escherichia coli strain BL21
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C62S
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inactive mutant, no Fe-S cluster formation
C66S
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inactive mutant, no Fe-S cluster formation
C69S
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inactive mutant, no Fe-S cluster formation
C71S
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inactive mutant, same Fe-S cluster formation as in wild-type HemN
E145A
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appears colorless, the [4Fe-4S] cluster content is slightly reduced, no detectable S-adenosylmethionine cleavage, no detectable CPO activity
E145I
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appears colorless, the [4Fe-4S] cluster content is slightly reduced, no detectable S-adenosylmethionine cleavage, no detectable CPO activity
F310A
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is slightly yellow, the [4Fe-4S] cluster content is slightly reduced, cleaves only one S-adenosylmethionine molecule per molecule protein, residual CPO activity
F310L
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is slightly yellow, the [4Fe-4S] cluster content is slightly reduced, cleaves only one S-adenosylmethionine molecule per molecule protein, no detectable CPO activity
F68L
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mutant with 89% of wild-type activity
G111V/G113V
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double mutation of Gly-111 and Gly-113, which are part of the potential GGGTP S-adenosyl-L-methionine binding motif, completely abolishes enzyme activity, reduced Fe-S cluster formation
H58L
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inactive mutant, no Fe-S cluster formation
I329A
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contains the same amount of iron-sulfur cluster as the wild-type HemN, but cleaves only one S-adenosylmethionine molecule per molecule protein, no detectable CPO activity; exhibits the same yellow-brown color as wild-type HemN, but the [4Fe-4S] cluster content is slightly reduced and cleaves only one S-adenosylmethionine molecule per molecule protein, no detectable CPO activity
Q311A
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contains the same amount of iron-sulfur cluster as the wild-type HemN, but cleaves only one S-adenosylmethionine molecule per molecule protein, no detectable CPO activity; exhibits the same yellow-brown color as wild-type HemN, but the [4Fe-4S] cluster content is slightly reduced and cleaves only one S-adenosylmethionine molecule per molecule protein, no detectable CPO activity
Y56A
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appears colorless, the [4Fe-4S] cluster content is slightly reduced, no detectable S-adenosylmethionine cleavage, no detectable CPO activity
Y56F
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mutant with 45% of wild-type activity and reduced Fe-S cluster formation
Y56L
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appears colorless, the [4Fe-4S] cluster content is slightly reduced, no detectable S-adenosylmethionine cleavage, no detectable CPO activity
additional information
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construction of deletion mutants of the HemN genes, growth of the mutant DELTAsll1876 is significantly slower than that of the wild-type under microoxic conditions, while it grows normally under aerobic conditions. Coproporphyrin III is accumulated at a low but significant level in the DELTAsll1876 mutant grown under micro-oxic conditions. No detectable phenotype in DELTAsll1917 under the conditions, phenotypes, overview
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant soluble His-tagged viperin (45-361) from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, recombinant His-tagged full-length enzyme and viperin (214-361) from Escherichia coli strain BL21 inclusion bodies is solubilized by 8 M urea and further renaturated and purificated by nickel affinity chromatography and gel filtration. Reconstitution of the [4Fe-4S] cluster in Viperin residues 45-361, overview
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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EPR spectrum of a potential substrate radical for HemN
pharmacology
the structure of HemN sets the stage for the development of inhibitors with antibacterial function due to the uniquely bacterial occurence of the enzyme
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