Information on EC 1.14.99.58 - heme oxygenase (biliverdin-IX-beta and delta-forming)

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The expected taxonomic range for this enzyme is: Pseudomonas

EC NUMBER
COMMENTARY hide
1.14.99.58
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RECOMMENDED NAME
GeneOntology No.
heme oxygenase (biliverdin-IX-beta and delta-forming)
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protoheme + 3 reduced acceptor + 3 O2 = biliverdin-IX-beta + CO + Fe2+ + 3 acceptor + 3 H2O
show the reaction diagram
(2)
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protoheme + 3 reduced acceptor + 3 O2 = biliverdin-IX-delta + CO + Fe2+ + 3 acceptor + 3 H2O
show the reaction diagram
(1)
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protoheme + 3 [reduced NADPH-hemoprotein reductase] + 3 O2 = biliverdin + Fe2+ + CO + 3 [oxidized NADPH-hemoprotein reductase] + 3 H2O
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
heme degradation III
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Porphyrin and chlorophyll metabolism
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SYSTEMATIC NAME
IUBMB Comments
protoheme,donor:oxygen oxidoreductase (biliverdin-IX-beta and delta-forming)
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene hemO; two genes pigA encoding PigA homologues
UniProt
Manually annotated by BRENDA team
; PigA; gene pigA
UniProt
Manually annotated by BRENDA team
; PigA; gene pigA
UniProt
Manually annotated by BRENDA team
two genes pigA encoding PigA homologues
UniProt
Manually annotated by BRENDA team
two genes pigA encoding PigA homologues
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
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the catalytic action of the enzyme drives the metabolic flux of extracellular heme uptake
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
heme + electron donor + O2
alpha-biliverdin + beta-biliverdin + delta-biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
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wild-type, mutant N19K, mutant F117Y, 30% beta- and 70% delta-isomer, N19K/F117Y double mutant, 55% alpha-, 10% beta-, 35% delta-isoform
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?
heme + electron donor + O2
biliverdin IXalpha + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
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prefers ferredoxin or ascorbate as electron donor
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?
protoheme + reduced acceptor + O2
biliverdin-IX-beta + CO + Fe2+ + acceptor + H2O
show the reaction diagram
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-
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-
?
protoheme + reduced acceptor + O2
biliverdin-IX-delta + CO + Fe2+ + acceptor + H2O
show the reaction diagram
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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
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
protoheme + reduced acceptor + O2
biliverdin-IX-beta + CO + Fe2+ + acceptor + H2O
show the reaction diagram
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-
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?
protoheme + reduced acceptor + O2
biliverdin-IX-delta + CO + Fe2+ + acceptor + H2O
show the reaction diagram
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ferredoxin-NADP+-oxidoreductase
additional information
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
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essential requirement
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-2-[4-(dimethylamino)benzylidene]hydrazinecarboximidamide
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binding affinity 0.030 mM
(2E)-2-[[4-(dimethylamino)phenyl]methylidene]hydrazinecarboximidamide
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binding affinity is 0.030 mM, complete inhibition
(2Z)-4-[(4-anilinophenyl)amino]-4-oxobut-2-enoic acid
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binding affinity 0.0201 mM, above 0.25 mM significant decrease in growth of strain on heme as sole source of iron
(2Z)-N'-[(1Z)-pyridin-3-ylmethylene]-2-(pyridin-3-ylmethylene)hydrazinecarboximidohydrazide
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binding affinity 0.0159 mM
(2Z)-N'-[(1Z)-pyridin-3-ylmethylidene]-2-(pyridin-3-ylmethylidene)hydrazinecarboximidohydrazide
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binding affinity is 0.0159 mM, complete inhibition
1-(2,4-dinitrophenyl)methanamine
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binding affinity 0.187 mM
2-(4-chlorophenyl)-N'-[(1E)-1H-indol-3-ylmethylidene]acetohydrazide
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binding affinity is 0.0158 mM, complete inhibition
2-(4-chlorophenyl)-N'-[(1Z)-1H-inden-3-ylmethylene]acetohydrazide
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binding affinity 0.0158 mM, above 0.25 mM significant decrease in growth of strain on heme as sole source of iron
4-oxo-4-[[4-(phenylamino)phenyl]amino]butanoic acid
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binding affinity is 0.0201 mM, complete inhibition
4-[(2-hydroxyphenyl)amino]naphthalene-1,2-dione
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binding affinity is 0.0728 mM, partial inhibition
N'-(pyridin-4-ylcarbonyl)pyridine-4-carbohydrazide
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binding affinity is 0.0447 mM, partial inhibition
N-(4-imidazo[1,2-a]pyridin-2-ylphenyl)-2-nitrobenzamide
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binding affinity is 0.0061 mM, complete inhibition
N-(4-imidazo[1,2-a]pyridin-2-ylphenyl)-3-nitrobenzamide
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binding affinity 0.0061 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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dependence of bphOP expression on RpoS
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0242 - 0.0269
heme
additional information
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21450
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x * 23000, SDS-PAGE, recombinant enzyme, x * 21450, deduced from gene sequence
23000
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x * 23000, SDS-PAGE, recombinant enzyme, x * 21450, deduced from gene sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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heme transfer to the enzyme is independent of heme affinity and is mediated via a specific protein-protein interaction. A spin transition is involved during the transfer process with spin-state crossover occuring in the heme binding protein PhuS prior to the heme transfer step or alternatively occuring within the enzyme. Activation energies at pH 7.5 for the heme transfer from PhuS to enzyme are about 12-14 kcal per mol
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Carr-Purcell-Meiboom-Gill NMR study on ferric enzyme state inhibited by cyanide and azide, and its ferrous state inhibited by carbon monoxide. The nature of the coordinated distal ligand affects the conformational freedom of the polypeptide in regions of the enzyme far removed from the heme iron and distal ligand. In addition to proton delivery to the nascent FeIII-OO- intermediate during catalysis, the hydrogen-bonding network serves to propagate the electronic state in each of the distinct steps of the catalytic cycle to key but remote sections of the polypeptide and to modulate the conformational freedom of the enzyme
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NMR-spectroscopy studies of paramagnetic cyanide-inhibited and azide-inhibited enzyme forms. The protein in the azide-inhibited complex is significantly less prone to H/D exchange than the cyanide-inhibited form. Unpaired spin delocalization from the heme iron into the G15-N atom via formation of a hydrogen bond between the coordinated azide nitrogen and the G125 N-H
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
53
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thermal tolerance of mutant strains, while a 10 min heat shock is already lethal to bphO and bphOP mutants, the wild-type strain still has a survival rate of 45%, overview
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme, pure enzyme solution has a bright green colour
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recombinant GST-tagged BphO from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography; recombinant GST-tagged PigA from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
recombinant GST-tagged BphO from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography; recombinant GST-tagged PigA from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography; recombinant GST-tagged PigA from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
O69002;, Q88P48;, Q9HWR4;
recombinant GST-tagged PigA from Escherichia coli strain BL21(DE3) by affinity chromatography; recombinant N-terminally His6-tagged BphO from Escherichia coli strain BL21(DE3) by affinity chromatography
recombinant GST-tagged PigA from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in a Neisseria meningitidis HemO deletion mutant
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expressed in Escherichia coli BL21(DE3) cells
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gene bphO, BphO is genetically coupled to the phytochrome BphP, expression of GST-tagged BphO in Escherichia coli strain BL21(DE3); gene pigA, pigA genes are organized in gene clusters associated with iron utilization, expression of GST-tagged PigA in Escherichia coli strain BL21(DE3)
gene bphO, BphO is genetically coupled to the phytochrome BphP, expression of GST-tagged BphO in Escherichia coli strain BL21(DE3); gene pigA, pigA genes are organized in gene clusters associated with iron utilization, expression of GST-tagged PigA in Escherichia coli strain BL21(DE3); genes pigA, two homologues, one of the two PigA homologues identified in Pseudomonas putida KT2440 is encoded in an iron-associated gene cluster, expression of GST-tagged PigA and BphO in Escherichia coli strain BL21(DE3)
O69002;, Q88P48;, Q9HWR4;
gene bphO, BphO is genetically coupled to the phytochrome BphP, expression of N-terminally His6-tagged BphO in Escherichia coli strain BL21(DE3); gene pigA, pigA genes are organized in gene clusters associated with iron utilization, expression of GST-tagged PigA in Escherichia coli strain BL21(DE3)
gene bphOP, DNA and amino acid sequence, including promoter, determination and analysis, expression analysis, dependence of bphOP expression on RpoS
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genes pigA, two homologues, one of the two PigA homologues identified in Pseudomonas putida KT2440 is encoded in an iron-associated gene cluster, expression of GST-tagged PigA and BphO in Escherichia coli strain BL21(DE3)
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F117Y
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no change in regioselectivity
F189A
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme. The mutant produces only beta- and delta-biliverdins, but no alpha-biliverdin
F189G
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme. The mutant produces only beta- and delta-biliverdins, but no alpha-biliverdin
F189L
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme. The mutant produces only beta- and delta-biliverdins, but no alpha-biliverdin
F189T
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme. The mutant produces only beta- and delta-biliverdins, but no alpha-biliverdin
G125V
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single-phase kinetics of transfer of heme from heme-binding protein PhuS
H26A/K34A/K132A
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inactive
K132A
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme, but the mutant produces 12% of alpha-biliverdin in addition to the formation of normal beta- (26%) and delta- (62%) biliverdins
K34A
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme, but the mutant produces 11% of alpha-biliverdin in addition to the formation of normal beta- (34%) and delta- (55%) biliverdins
K34A/K132A
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme, but the mutant produces 18% of alpha-biliverdin in addition to the formation of normal beta- (27%) and delta- (56%) biliverdins
N19K
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no change in regioselectivity
N19K/F117Y
N19K/F117Y/K132A
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destabilization of heme within the protein, transfer of heme from heme binding protein PhuS is not affected and shows biphasic kinetics
N19K/F117Y/K34N
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destabilization of heme within the protein, transfer of heme from heme binding protein PhuS is not affected and shows biphasic kinetics
N19K/K34A/F117Y/K132A
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the mutant produces biliverdin-IX-alpha
R80L
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mutant exhibits allmost global conformational disorder related to significantly lower efficiency to hydroxylate heme in the presence of H2O2
T189W
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the heme degradation activity of the mutant is similar to that of the wild-type enzyme. The mutant produces only beta- and delta-biliverdins, but no alpha-biliverdin
additional information
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chromosomal knock-out gene bphO mutants shows identical growth behavior as the wild type under various conditions, the bphO mutant and the double mutant strain DELTAbphO show increased levels of pyocyanin, as well as decreased heat tolerance in the stationary phase, phenotypes, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
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the enzyme is a potential therapeutic target for antimicrobial drug development, computer-aided drug design and screening, overview