Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 1.14.14.18 - heme oxygenase (biliverdin-producing) and Organism(s) Homo sapiens and UniProt Accession P30519

for references in articles please use BRENDA:EC1.14.14.18
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
This mammalian enzyme participates in the degradation of heme. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules . The third oxygen molecule provides the oxygen atom that converts the alpha-carbon to CO. The enzyme requires NAD(P)H and EC 1.6.2.4, NADPH---hemoprotein reductase. cf. EC 1.14.15.20, heme oxygenase (biliverdin-producing, ferredoxin).
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: P30519
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
heme oxygenase-1, heme oxygenase, hmox1, heme oxygenase 1, haem oxygenase, hsp32, heme oxygenase-2, hmox2, heme oxygenase 2, hmox1a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heme oxygenase 2
-
heme oxygenase-2
-
haem oxygenase
-
-
-
-
heme oxygenase
-
-
heme oxygenase 1
-
-
heme oxygenase-1
heme oxygenase-2
-
-
Hmox1
inducible heme oxygenase-1
-
ORP33 proteins
-
-
-
-
oxygenase, heme (decyclizing)
-
-
-
-
proteins, specific or class, ORP33 (oxygen-regulated protein 33,000-mol.-wt.)
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protoheme + 3 [reduced NADPH-hemoprotein reductase] + 3 O2 = biliverdin + Fe2+ + CO + 3 [oxidized NADPH-hemoprotein reductase] + 3 H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
protoheme,NADPH-hemoprotein reductase:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating)
This mammalian enzyme participates in the degradation of heme. The terminal oxygen atoms that are incorporated into the carbonyl groups of pyrrole rings A and B of biliverdin are derived from two separate oxygen molecules [4]. The third oxygen molecule provides the oxygen atom that converts the alpha-carbon to CO. The enzyme requires NAD(P)H and EC 1.6.2.4, NADPH---hemoprotein reductase. cf. EC 1.14.15.20, heme oxygenase (biliverdin-producing, ferredoxin).
CAS REGISTRY NUMBER
COMMENTARY hide
9059-22-7
-
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 + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
protoheme + [reduced cytochrome P450 reductase] + O2
biliverdin + Fe2+ + CO + [oxidized cytochrome P450 reductase] + H2O
show the reaction diagram
-
-
-
?
15-phenylheme + electron donor + O2
10-phenylbiliverdin IXalpha + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
?
5-phenylheme + electron donor + O2
biliverdin IXalpha + Fe2+ + CO + oxidized eletron donor + H2O + benzoic acid
show the reaction diagram
-
-
-
?
alpha-meso-formylmesoheme + NADPH
? + NADP+
show the reaction diagram
-
exclusively oxidized at a non-formyl substituted meso-carbon
-
?
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized electron donor + H2O
show the reaction diagram
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
heme + NADPH + H+ + O2
biliverdin IXalpha + Fe2+ + CO + NADP+ + H2O
show the reaction diagram
-
wild-type, selective production of biliverdin IXalpha
-
?
heme + NADPH + H+ + O2
biliverdin IXdelta + biliverdin IXalpha + Fe2+ + CO + NADP+ + H2O
show the reaction diagram
-
mutant R183E, yields about 20% of product biliverdin IXdelta
-
?
methemoglobin + electron donor + O2
?
show the reaction diagram
-
-
-
-
?
protoheme + [reduced cytochrome P450 reductase] + O2
biliverdin + Fe2+ + CO + [oxidized cytochrome P450 reductase] + H2O
show the reaction diagram
-
-
-
?
protoheme + [reduced NADPH-hemoprotein reductase] + H+ + O2
biliverdin-IX-alpha + CO + Fe2+ + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
protoheme + [reduced NADPH-hemoprotein reductase] + O2
biliverdin + Fe2+ + CO + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL 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 + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
involved in heme metabolism
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
protoheme + [reduced NADPH-hemoprotein reductase] + H+ + O2
biliverdin-IX-alpha + CO + Fe2+ + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
protoheme + [reduced NADPH-hemoprotein reductase] + O2
biliverdin + Fe2+ + CO + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
CO as a ferrous heme ligand or ferricyanide as an oxidant have no effect
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
chromium protoporphyrin
-
-
tin protoporphyrin
-
zinc protoporphyrin
low inhibition
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0015 mM
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulphanyl)methyl]-1,3-dioxolane
-
(2S, 4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((4-aminophenyl)thio)methyl]-1,3-dioxolane
azalanstat, potent inhibitor of HO
1,10-phenanthroline
-
weak
1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone
-
1-(4-bromophenyl)-2-[2-(1-methylethyl)-1H-imidazol-1-yl]ethanone
27% inhibition at 0.1 mM
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
1-[4-(3-bromophenoxy)butyl]-1H-imidazole
54% inhibition at 0.1 mM
2,2'-dipyridyl
-
weak
2-[2-(4-bromophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
2-[2-(4-fluorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl)methyl]1,3-dioxolane
-
4-hydroxymercuribenzoate
-
-
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
4-phenyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one
-
4-phenyl-1-(1H-imidazol-1-yl)-2-butanone
-
azalanstat
benzyl isocyanide
-
most potent uncompetitive inhibitor with respect to heme, is the strongest ligand to ferrous heme with an almost 42fold greater binding affinity for HO-1 than isopropyl isocyanide. HO-2 displays a similar trend. Ferric verdoheme-HO-1 shows a 2fold higher affinity for the inhibitor than ferric heme-HO-1
chromium protoporphyrin
-
-
Co-protoporphyrin
-
0.005 mM, 82.5% inhibition of kidney heme oxygenase
Co2+
-
0.4 mM, significant inhibition
cobalt protoporphyrin
i.e. CoPP, significantly reduces the viability of glioma cells GBM8401 in the absence of serum, fetal bovine serum or bovine serum albumin completely abolishes the cytotoxic effect, overview, N-acetyl-l-cysteine does not protect against cell death
copoly(styrene-maleic acid)-zinc protoporphyrin
micelles, competitive inhibition
Cu2+
-
0.2 mM, significant inhibition
cysteine
-
-
DTE
-
shows high-affinity binding, structure, overview
DTT
-
shows high-affinity binding, structure, overview. The noncoordinating thiol group of DTT is critical for its high affinity to the mammalian HO
EDTA
-
weak
Fe-deuteroporphyrin IX 2,4-bisglycol
-
0.01 mM, 46.8% inhibition of kidney heme oxygenase
ferric protoporphyrin
i.e. FePP or hemin, significantly reduces the viability of glioma cells GBM8401 in the absence of serum, fetal bovine serum or bovine serum albumin completely abolishes the cytotoxic effect, overview, N-acetyl-l-cysteine protects against cell death
isopropyl isocyanide
-
binding affinity is the weakest for HO-1. HO-2 displays a similar trend
KCN
-
strong inhibition
n-butyl isocyanide
-
displays a 9fold higher affinity than isopropyl isocyanide for HO-1. HO-2 displays a similar trend. Ferric verdoheme-HO-1 shows a 2fold higher affinity for the inhibitor than ferric heme-HO-1
NaN3
-
strong inhibition
pegylated zinc protoporphyrin
inhibition of isozyme HO-1
Porphyrins
-
Zn-deuteroporphyrin IX 2,4-bis glycol, synthetic metal porphyrins
Sn-protoporphyrin
-
0.005 mM, complete inhibition of kidney heme oxygenase
Sn-protoporphyrin IX
i.e. SNPPIX
thioglycerol
-
binds with 10fold lower affinity than DTT, shows high affinity to the mammalian HO
tin protoporphyrin
tin protoporphyrin IX
-
zinc protoporphyrin
zinc protoporphyrin IX
-
zinc(II) deuteroporphyrin IX-2, 4-bisethyleneglycol
-
Zn(II) protoporphyrin IX
i.e. ZnPP
Zn-deuteroporphyrin IX 2,4-bisglycol
-
0.002 mM, complete inhibition of kidney heme oxygenase
Zn-protoporphyrin
-
0.005 mM, 93.4% inhibition of kidney heme oxygenase
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7 - 15.2
[reduced cytochrome P450 reductase]
-
0.003 - 0.018
heme
0.0164
protoheme IX
-
enzyme from spleen
0.5 - 21.7
[reduced cytochrome P450 reductase]
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015
benzyl isocyanide
-
HO-1
0.00012
copoly(styrene-maleic acid)-zinc protoporphyrin
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
Homo sapiens
-
IC50: 0.0015 mM
0.0021
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane
0.00027
1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone
Homo sapiens
pH and temperature not specified in the publication
0.00014
2-[2-(4-bromophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
Homo sapiens
pH and temperature not specified in the publication
0.0005
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
Homo sapiens
pH and temperature not specified in the publication
0.0014
2-[2-(4-fluorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
Homo sapiens
pH and temperature not specified in the publication
0.0062
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
Homo sapiens
pH and temperature not specified in the publication
0.00076
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl)methyl]1,3-dioxolane
Homo sapiens
pH and temperature not specified in the publication
0.0025 - 0.089
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
0.00406
4-phenyl-1-(1H-imidazol-1-yl)-2-butanone
Homo sapiens
pH and temperature not specified in the publication
0.0001 - 0.005
benzyl isocyanide
0.017 - 1.2
DTE
0.00072 - 0.00117
isopropyl isocyanide
0.00025 - 0.045
n-butyl isocyanide
additional information
additional information
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00000625
-
activity in kidney microsomes, micromol bilirubin/min/mg
0.017
-
28000 Da recombinant tryptic fragment of heme oxygenase-2
0.024
-
recombinant C-terminal truncated heme oxygenase-1
0.0705
purified recombinant wild-type enzyme
0.101
purified recombinant HO-1 mutant R254K
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9
-
binding capacity increases with the increasing pH from 7 to 9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
isozyme HO-2
Manually annotated by BRENDA team
high activity
Manually annotated by BRENDA team
isozyme HO-2
Manually annotated by BRENDA team
-
high HO-1 expression
Manually annotated by BRENDA team
-
in vivo, high HO-1 expression. HO-1 protein is strongly expressed in proliferative, Ki67-positive cytotrophoblasts of cell columns. HO-1 is strongly expressed in cycling cytotrophoblasts of first trimester explant cultures
Manually annotated by BRENDA team
HCV-infected liver biopsies and core protein-expressing hepatocytes show diminished levels of heme oxygenase-1
Manually annotated by BRENDA team
a fibrosarcoma cell line
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
a breast carcinoma
Manually annotated by BRENDA team
an ovarian carcinoma cell line
Manually annotated by BRENDA team
quantitative HO-1 expression analysis
Manually annotated by BRENDA team
a pancreatic cancer cell line
Manually annotated by BRENDA team
-
oral tissue
Manually annotated by BRENDA team
-
HLA-A2/HO-1-restricted, CD8+ T cells in peripheral blood lymphocytes of cancer patients
Manually annotated by BRENDA team
-
activity is very low in obstructive azoospermia specimens, low in nonobstructive azoospermia, moderate in oligozoospermia while higher in normozoospermia. HO-2 expression in all studied groups whereas HO-1 is highly expressed in fertile normozoospermic group compared with other groups
Manually annotated by BRENDA team
obtained from the knee joints at the time of joint surgery or synovectomy, performed as a normal part of clinical care, from 20 rheumatoid arthritis patients, HO-1 expression analysis
Manually annotated by BRENDA team
a monocytic leukaemia cell line
Manually annotated by BRENDA team
quantitative HO-1 expression analysis
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
evolution
bacterial HmuO and mammalian heme oxygenases are similar in their reaction mechanisms and structures
malfunction
mutation of the distal Asp decreases the verdoheme ring opening activity
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
HMOX2_HUMAN
316
1
36033
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36500
x * 36500, isozyme HO-2
28000
-
x * 28000, wild-type and mutant, SDS-PAGE
30500
-
x * 30500, SDS-PAGE
32000
36000
-
x * 36000, recombinant heme oxygenase-2, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 36500, isozyme HO-2
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
HO-1 contains several thrombin cleavage sites, one of which is located at the C-terminus to cleave the membrane binding domain, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apo- and heme-bound truncated HO-2, lacking the three heme regulatory motifs and the membrane binding region, apo-HO-2: hanging drop method, 0.0015 ml of 5 mg/ml protein in 50 mM KCl, 50 mM Tris-HCl, pH 7.5, are mixed with 0.001 ml of well solution containing 40% PEG 1500, 200 mM potassium glutamate, and 100 mM triethanolamine, pH 8.5, at 4°C, heme-bound HO-2: hanging drop vapour diffusion method, 0.0015 ml of 5 mg/ml protein in 50 mM KCl, 50 mM Tris-HCl, pH 7.5, are mixed with 0.001 ml of well solution containing 33% PEG dimethlyether 500, 20 mM MgCl2, and 100 mM HEPES, pH 8.5, at 4°C, X-ray diffraction structure determination and analysis at 2.4 A resolution for the apoenzyme, and at 2.6 A resolution for the heme-bound enzyme
apo-enzyme and in complex with heme
-
crystal structure determination and analysis of HO-1 in complex with different inhibitors, i.e. 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane, (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane, 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone, 4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one, and 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone, overview
heme oxygenase HO1 complexed with reaction intermediate verdoheme, and in tertiary complex with verdoheme and NO, X-ray diffraction structure determination and analysis at 2.2 and 2.1 A resolution, respectively
heme oxygenase-1
-
HO-1 in complex with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone to a resolution of 1.54 A, the coordinating nitrogen atom of His25 is shifted by 0.91 A while the Fe moiety is shifted by 0.85 A. Distal pocket of in the complex is more-open than that of the native holoenzyme. HO-1 in complex with 4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one to a resolution of 2.20 A, or in complex with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane
HO-1 in complex with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone, by sitting-drop vapor diffusion method, at room temperature, to 1.5 A resolution. Overall structure of the HO-1-inhibitor complex is very similar to that of the native heme-conjugated HO-1, being mostly alpha-helical with the heme sandwiched between the proximal and distal helices. The inhibitor binds to the HO-1 distal pocket such that the imidazolyl moiety coordinates with heme iron while the adamantyl group is stabilized by a hydrophobic binding pocket. Distal helix flexibility, coupled with shifts in proximal residues and heme, acts to expand the distal pocket, thus accommodating the bulky inhibitor without displacing heme. Inhibitor binding effectively displaces the catalytically critical distal water ligand
in complex with 5-phenylheme or 15-phenylheme
in complex with biliverdin
-
in complex with ferrous and ferrous-NO forms of verdoheme, absence of network of water-molecules in both structures
mutant H25R with bound heme, to 2.95 A resolution. Contrary to wild-type, the Arg25 side-chain in the H25R mutant is oriented away from the parent His25 position, accompanied by reorientation of the Glu29 side-chain
mutant R183E
sitting drop vapour diffusion method
wild-type and mutant H25A, by hanging drop vapor diffusion method, at 2.8 A resolution. Mutant heme-HO-1 crystal is monoclinic, space group P21, there are four molecules in an asymmetric unit cell. The molecular surfaces of wild-type and mutant are of little difference, though the active pocket in the mutant is larger. The two have the same substrate affinity in electrostatic potential. A positive charge region on the edge of heme forms around the catalytic reaction pocket. After mutation, Ala is still located in the surface and does not influence the electrostatic potential of the reaction pocket
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K169A
22fold increase in Km values for cytochrome P450 reductase
L201A
3fold increase in Km values for cytochrome P450 reductase
R87A
1.3fold increase in Km values for cytochrome P450 reductase
C127A
-
site-directed mutagenesis of the truncated HO-2 variant lacking the membrane spanning domain, spectral properties in comparison to the wild-type HO-2, overview
C127A/C282A
-
site-directed mutagenesis of the truncated HO-2 variant lacking the membrane spanning domain, spectral properties in comparison to the wild-type HO-2, overview
D140A
D140H
0.5% activity compared to the wild type enzyme
D140K
7.1% activity compared to the wild type enzyme
E29K
26% activity compared to the wild type enzyme
G139A
retains about 60% of the wild type HO activity
G143H
the replacement of Gly143 with His leads to the formation of a bis-histidine complex
H132A
-
heme oxygenase-1, 40-50% of wild-type activity
H132G
-
heme oxygenase-1, 40-50% of wild-type activity
H132S
-
heme oxygenase-1, 20% of wild-type activity
H20A
-
-
H25M/E29A
mutant retains activity
H25R
crystallization analysis
H25R/E29A
mutant retains activity
K149
42fold increase in Km values for cytochrome P450 reductase
K18A
114% activity compared to the wild type enzyme
K18A/R183E
2% activity compared to the wild type enzyme
K18A/Y134F/R183E
2% activity compared to the wild type enzyme
K18E
92% activity compared to the wild type enzyme
K18E/E29K/R183E
1.2% activity compared to the wild type enzyme
K18E/R183E
3% activity compared to the wild type enzyme
R183a
24% activity compared to the wild type enzyme
R183E
R254K
Y134F
76% activity compared to the wild type enzyme
Y134F/R183E
2.8% activity compared to the wild type enzyme
Y58A
46% activity compared to the wild type enzyme
Y58A/D140A
13% activity compared to the wild type enzyme
Y58F
38% activity compared to the wild type enzyme
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10.3
-
sequential Ni-Ni+1 connections for Ile57-Ala60, His84-Lys86, Leu93-Trp96, and Leu164-Phe167 can be observed even at pH 10.3, with chemical shift similar to those for heme oxygenase-2,4-dimethyldeuterohemin-H2O
702262
6 - 6.5
-
truncated HO-1 does not bind on the adsorbent at low pH 6 and 6.5
672651
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 4
-
several hours
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant GST-tagged wild-type and mutant HO-2 from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
ammonium sulfate, Sephadex G-75, DEAE-cellulose, hydroxyapatite, tryptic 28000 Da fragment of recombinant heme oxygenase-2
-
DEAE-ion exchange expanded bed adsorption and Superdex 75 gel filtration, the specific HO-1 activity increases from 0.82 to 24.8 U/mg during purification steps
-
deletion of 23 C-terminal amino acids, which serve as the membrane-spanning domain, allows for a rapid purification of truncated, soluble HO-1 in large quantities, by standard column chromatography
-
on anion-exchange column
on Ni-NTA column, wild-type 32fold purified and mutant H25A 31fold purified, more than 95% pure
-
partial
-
recombinant C-terminal truncated heme oxygenase-1, ammonium sulfate, Mono Q, recombinant heme oxygenase-1/cytochrome P450 reductase fusion protein, ammonium sulfate, 2',5'-ADP-Sepharose
-
recombinant GST-tagged full-length HO-1 mutant R254K 54fold and recombinant wild-type enzyme 40fold by thrombin treatment and glutathione affinity chromatography, elution with 1.0% sarkosyl detergent and 2% octyl glucoside, the recombinant wild-type full-length enzyme is not stable during expression and purification due to proteolytic cleavage, overview
truncated HO-1 and HO-2 lacking the 23 C-terminal residues, by gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of GST-tagged wild-type and mutant HO-2 in Escherichia coli strain BL21(DE3)
265-residue constructs of wild-type and mutant D140A
-
293FT cells transiently cotransfected with a vector containing the viral packaging proteins gag and pol, a vector containing env and pMSCV-scrttaM2puro or pRevTRE-hHO1
-
710-bp fragment encoded amino acids of wild-type and mutant HO-1 constructed in the plasmids pET28b(+)-hHO-1(w) and (m), expressed in Escherichia coli BL21 (DE3)
-
adenovirus-mediated HO-1 transfection of Rattus norvegicus primary cardiomyocytes and H9C2 myocytes
-
expressed in Escherichia coli DH 5a cells
-
expression in Escherichia coli
expression in SH-SY5Y cells
expression of C-terminal truncated heme oxygenase-1 and of a heme oxygenase-1 cytochrome P450 reductase fusion protein
-
expression of GST-tagged full-length HO-1 mutant R254K and of GST-tagged wild-type enzyme in Escherichia coli strain DH5alpha
expression of heme oxygenase-2 in Escherichia coli
-
HO-1 expression analysis by real-time PCR
HO-1, DNA and amino acid sequence determination, quantitative expression analysis, overview
quantitative enzyme expression analysis
truncated HO-1 lacking the 23 C-terminal residues, truncated HO-2 lacking the 23 C-terminal residues in the pBAce expression vector construct transformed into Escherichia coli DH5alpha
-
truncated human HO-1 expression vector, expressed in Escherichia coli strain DH5alpha
-
truncated, soluble version of HO-1 that contains 233 amino acids expressed from plasmid HO1-t233/pBace in Escherichia coli DH5alpha
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
21 h treatment with 0.05-0.2 mM docosahexaenoic acid enhances isoform HO-1 expression through transcriptional regulation in human cancer cells. Docosahexaenoic acid induces Bach1 protein degradation, thereby enhancing the transcriptional factor Nrf2-mediated isoform HO-1 gene transcription
-
apoptotic cell supernatants provoke a biphasic up-regulation of HO-1. Although the first phase of HO-1 induction at 6 h is accomplished by apoptotic cell-derived sphingosine-1-phosphate acting via sphingosine-1-phosphate receptor 1, the second wave of HO-1 induction at 24 h is attributed to autocrine signaling of vascular endothelial growth factor A, whose expression and release are facilitated by sphingosine-1-phosphate
-
HO-1 activity is upregulated in response to several therapeutic treatments and is implicated in promoting tumour growth
HO-1 expression is chemically induced by cobalt protoporphyrin-IX in HEK293 T-RExTM Nox4 cells resulting in downregulation of NADPH oxidase Nox4 activity
HO-1 expression is induced by cobalt protoporphyrin and andrographolide
HO-1 expression is reduced upon differentiation of cytotrophoblasts into extravillous trophoblasts. Knock down of endogenous HO-1 in BeWo cells using retroviral transduction with a miRNA adapted retroviral vector targeting human HO-1 sequence
-
HO-1 protein expression is strongly induced 24 h after DOX addition in the HTR-8/SVneo cell line
-
lipopolysaccharide downregulates isoform HO-1 in primary human peripheral blood mononuclear cells, CD14+ monocytes, macrophages, dendritic cells, and granulocytes
-
lipopolysaccharide upregulates isoform HO-1 in human monocytic leukemia cell lines. Bach1 is a critical transcriptional repressor of isoform HO-1
-
low concentration of 4-hydroxy hexenal increases heme oxygenase-1 expression through activation of Nrf2 and antioxidative activity in vascular endothelial cells, overview. The induction is abolished by knockout of Nrf2
-
oxidative stress promotes enzyme up-regulation
-
small interfering RNA-mediated knock-down of Nrf-2 significantly inhibits surfactin-induced HO-1 expression. Inhibition of phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase significantly decreased surfactin-induced HO-1 expression, mechanism of surfactin, overview
-
surfactin, a cyclic lipopeptide produced by Bacillus subtilis, induces HO-1 mRNA and protein expression via activation of Nrf2, and PI3K/Akt and ERK, mechanism of surfactin, overview. Nrf-2 is a redox-sensitive basic-leucine zipper transcription factor
-
systemic enzyme levels are dramatically increased in individuals with active pulmonary and extra-pulmonary tuberculosis and particularly those with bilateral lung lesions and elevated bacillary loads in sputum
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
live-cell activity assay based on heterologous coexpression in Escherichia coli of heme oxygenase and its mutants and a fluorescent biliverdin biosensor
drug development
heme oxygenase has cytoprotective properties and may play a role in several disease states, making it an interesting therapeutic target
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schacter, B.A.
Assay of microsomal heme oxygenase in liver and spleen
Methods Enzymol.
52
367-372
1978
Bos taurus, Gallus gallus, Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Matasek, P.; Solangi, K.; Goodman, A.I.; Levere, R.D.; Chernick, R.J.; Abraham, N.G.
Properties of human kidney heme oxygenase: inhibition by synthetic heme analogues and metalloporphyrins
Biochem. Biophys. Res. Commun.
157
480-487
1988
Homo sapiens
Manually annotated by BRENDA team
Ishikawa, K.; Takeuchi, N.; Takahashi, S.; Matera, K.M.; Sato, M.; Shibahara, S.; Rousseau, D.L.; Ikeda-Saito, M.; Yoshida, T.
Heme oxygenase-2. Properties of the heme complex of the purified tryptic fragment of recombinant human heme oxygenase-2
J. Biol. Chem.
270
6345-6350
1995
Homo sapiens
Manually annotated by BRENDA team
Wilks, A.; Black, S.M.; Miller, W.L.; Ortiz de Montellano, P.R.
Expression and characterization of truncated human heme oxygenase (hHO-1) and a fusion protein of hHO-1 with human cytochrome P450 reductase
Biochemistry
34
4421-4427
1995
Homo sapiens
Manually annotated by BRENDA team
Wilks, A.; de Montellano, P.R.O.; Sun, J.; Loehr, T.M.
Heme oxygenase (HO-1): His-132 stabilizes a distal water ligand and assists catalysis
Biochemistry
35
930-936
1996
Homo sapiens
Manually annotated by BRENDA team
Torpey, J.; Ortiz de Montellano, P.R.
Oxidation of alpha-meso-formylmesoheme by heme oxygenase. Electronic control of the reaction regiospecificity
J. Biol. Chem.
272
22008-22014
1997
Homo sapiens
Manually annotated by BRENDA team
Schuller, D.J.; Wilks, A.; De Montellano, P.R.O.; Poulos, T.L.
Crystal structure of human heme oxygenase-1
Nat. Struct. Biol.
6
860-867
1999
Homo sapiens
Manually annotated by BRENDA team
Wilks, A.; Moenne-Loccoz, P.
Identification of the proximal ligand His-20 in heme oxygenase (Hmu O) from Corynebacterium diphtheriae. Oxidative cleavage of the heme macrocycle does not require the proximal histidine
J. Biol. Chem.
275
11686-11692
2000
Corynebacterium diphtheriae, Homo sapiens
Manually annotated by BRENDA team
Liu, Y.; Ortiz de Montellano, P.R.
Reaction intermediates and single turnover rate constants for the oxidation of heme by human heme oxygenase-1
J. Biol. Chem.
275
5297-5307
2000
Homo sapiens
Manually annotated by BRENDA team
Lad, L.; Friedman, J.; Li, H.; Bhaskar, B.; Ortiz de Montellano, P.R.; Poulos, T.L.
Crystal structure of human heme oxygenase-1 in a complex with biliverdin
Biochemistry
43
3793-3801
2004
Homo sapiens
Manually annotated by BRENDA team
Lad, L.; Schuller, D.J.; Shimizu, H.; Friedman, J.; Li, H.; Ortiz de Montellano, P.R.; Poulos, T.L.
Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1
J. Biol. Chem.
278
7834-7843
2003
Homo sapiens
Manually annotated by BRENDA team
Wang, J.; Niemevz, F.; Lad, L.; Huang, L.; Alvarez, D.E.; Buldain, G.; Poulos, T.L.; de Montellano, P.R.
Human heme oxygenase oxidation of 5- and 15-phenylhemes
J. Biol. Chem.
279
42593-42604
2004
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Wang, J.; Lad, L.; Poulos, T.L.; Ortiz de Montellano, P.R.
Regiospecificity determinants of human heme oxygenase: differential NADPH- and ascorbate-dependent heme cleavage by the R183E mutant
J. Biol. Chem.
280
2797-2806
2005
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Lad, L.; Ortiz de Montellano, P.R.; Poulos, T.L.
Crystal structures of ferrous and ferrous-NO forms of verdoheme in a complex with human heme oxygenase-1: Catalytic implications for heme cleavage
J. Inorg. Biochem.
98
1686-1695
2004
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Xia, Z.W.; Zhou, W.P.; Cui, W.J.; Zhang, X.H.; Shen, Q.X.; Li, Y.Z.; Yu, S.C.
Structure prediction and activity analysis of human heme oxygenase-1 and its mutant
World J. Gastroenterol.
10
2352-2356
2004
Homo sapiens
Manually annotated by BRENDA team
Wang, J.; Evans, J.P.; Ogura, H.; La Mar, G.N.; Ortiz de Montellano, P.R.
Alteration of the regiospecificity of human heme oxygenase-1 by unseating of the heme but not disruption of the distal hydrogen bonding network
Biochemistry
45
61-73
2006
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Hu, H.B.; Wang, W.; Han, L.; Zhou, W.P.; Zhang, X.H.
An improved method for purification of recombinant truncated heme oxygenase-1 by expanded bed adsorption and gel filtration
Bioprocess Biosyst. Eng.
30
87-90
2007
Homo sapiens
Manually annotated by BRENDA team
Lad, L.; Koshkin, A.; de Montellano, P.R.; Poulos, T.L.
Crystal structures of the G139A, G139A-NO and G143H mutants of human heme oxygenase-1. A finely tuned hydrogen-bonding network controls oxygenase versus peroxidase activity
J. Biol. Inorg. Chem.
10
138-146
2005
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Vlahakis, J.Z.; Kinobe, R.T.; Bowers, R.J.; Brien, J.F.; Nakatsu, K.; Szarek, W.A.
Imidazole-dioxolane compounds as isozyme-selective heme oxygenase inhibitors
J. Med. Chem.
49
4437-4441
2006
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Muz, B.; Kontny, E.; Marcinkiewicz, J.; Maslinski, W.
Heme oxygenase-1 participates in the anti-inflammatory activity of taurine chloramine
Amino Acids
35
397-402
2008
Homo sapiens (P09601)
Manually annotated by BRENDA team
Joung, E.J.; Li, M.H.; Lee, H.G.; Somparn, N.; Jung, Y.S.; Na, H.K.; Kim, S.H.; Cha, Y.N.; Surh, Y.J.
Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target
Antioxid. Redox Signal.
9
2087-2098
2007
Homo sapiens (P09601)
Manually annotated by BRENDA team
Kroenke, G.; Kadl, A.; Ikonomu, E.; Blueml, S.; Fuernkranz, A.; Sarembock, I.J.; Bochkov, V.N.; Exner, M.; Binder, B.R.; Leitinger, N.
Expression of heme oxygenase-1 in human vascular cells is regulated by peroxisome proliferator-activated receptors
Arterioscler. Thromb. Vasc. Biol.
27
1276-1282
2007
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Lin, C.C.; Liu, X.M.; Peyton, K.; Wang, H.; Yang, W.C.; Lin, S.J.; Durante, W.
Far infrared therapy inhibits vascular endothelial inflammation via the induction of heme oxygenase-1
Arterioscler. Thromb. Vasc. Biol.
28
739-745
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Ogborne, R.M.; Rushworth, S.A.; OConnell, M.A.
Epigallocatechin activates haem oxygenase-1 expression via protein kinase Cdelta and Nrf2
Biochem. Biophys. Res. Commun.
373
584-588
2008
Homo sapiens (P09601)
Manually annotated by BRENDA team
Huber, W.J.; Backes, W.L.
Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase
Biochemistry
46
12212-12219
2007
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Iyer, A.K.; Greish, K.; Fang, J.; Murakami, R.; Maeda, H.
High-loading nanosized micelles of copoly(styrene-maleic acid)-zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor
Biomaterials
28
1871-1881
2007
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Nowis, D.; Bugajski, M.; Winiarska, M.; Bil, J.; Szokalska, A.; Salwa, P.; Issat, T.; Was, H.; Jozkowicz, A.; Dulak, J.; Stoklosa, T.; Golab, J.
Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent antitumor effects but is unable to potentiate antitumor effects of chemotherapeutics in mice
BMC Cancer
8
197
2008
Homo sapiens (P09601), Homo sapiens, Mus musculus (P14901), Mus musculus
Manually annotated by BRENDA team
Kinobe, R.T.; Dercho, R.A.; Nakatsu, K.
Inhibitors of the heme oxygenase - carbon monoxide system: on the doorstep of the clinic?
Can. J. Physiol. Pharmacol.
86
577-599
2008
Mus musculus (O70252), Mus musculus (P14901), Homo sapiens (P09601), Homo sapiens (P30519)
Manually annotated by BRENDA team
Wen, F.; Brown, K.E.; Britigan, B.E.; Schmidt, W.N.
Hepatitis C core protein inhibits induction of heme oxygenase-1 and sensitizes hepatocytes to cytotoxicity
Cell Biol. Toxicol.
24
175-188
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Kim, K.M.; Pae, H.O.; Zheng, M.; Park, R.; Kim, Y.M.; Chung, H.T.
Carbon monoxide induces heme oxygenase-1 via activation of protein kinase R-like endoplasmic reticulum kinase and inhibits endothelial cell apoptosis triggered by endoplasmic reticulum stress
Circ. Res.
101
919-927
2007
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Jeong, G.S.; Pae, H.O.; Jeong, S.O.; Kim, Y.C.; Kwon, T.O.; Lee, H.S.; Kim, N.S.; Park, S.D.; Chung, H.T.
The alpha-methylene-gamma-butyrolactone moiety in dehydrocostus lactone is responsible for cytoprotective heme oxygenase-1 expression through activation of the nuclear factor E2-related factor 2 in HepG2 cells
Eur. J. Pharmacol.
565
37-44
2007
Homo sapiens (P09601)
Manually annotated by BRENDA team
Pae, H.O.; Jeong, G.S.; Jeong, S.O.; Kim, H.S.; Kim, S.A.; Kim, Y.C.; Yoo, S.J.; Kim, H.D.; Chung, H.T.
Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells
Exp. Mol. Med.
39
267-277
2007
Rattus norvegicus (P06762), Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Chen, N.; Shao, W.; Lv, P.; Zhang, S.; Chen, Y.; Zhu, L.; Lu, Y.; Shen, Y.
Hemin-induced Erk1/2 activation and heme oxygenase-1 expression in human umbilical vein endothelial cells
Free Radic. Res.
41
990-996
2007
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Frank, J.; Lornejad-Schaefer, M.R.; Schoeffl, H.; Flaccus, A.; Lambert, C.; Biesalski, H.K.
Inhibition of heme oxygenase-1 increases responsiveness of melanoma cells to ALA-based photodynamic therapy
Int. J. Oncol.
31
1539-1545
2007
Homo sapiens (P09601)
Manually annotated by BRENDA team
Gruber, F.; Oskolkova, O.; Leitner, A.; Mildner, M.; Mlitz, V.; Lengauer, B.; Kadl, A.; Mrass, P.; Kroenke, G.; Binder, B.R.; Bochkov, V.N.; Leitinger, N.; Tschachler, E.
Photooxidation generates biologically active phospholipids that induce heme oxygenase-1 in skin cells
J. Biol. Chem.
282
16934-16941
2007
Homo sapiens (P09601)
Manually annotated by BRENDA team
Lee, G.H.; Kim, H.K.; Chae, S.W.; Kim, D.S.; Ha, K.C.; Cuddy, M.; Kress, C.; Reed, J.C.; Kim, H.R.; Chae, H.J.
Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen species and heme oxygenase-1 expression
J. Biol. Chem.
282
21618-21628
2007
Homo sapiens (P09601)
Manually annotated by BRENDA team
Bianchetti, C.M.; Yi, L.; Ragsdale, S.W.; Phillips, G.N.
Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2
J. Biol. Chem.
282
37624-37631
2007
Homo sapiens (P30519), Homo sapiens
Manually annotated by BRENDA team
Koizumi, S.; Gong, P.; Suzuki, K.; Murata, M.
Cadmium-responsive element of the human heme oxygenase-1 gene mediates heat shock factor 1-dependent transcriptional activation
J. Biol. Chem.
282
8715-8723
2007
Homo sapiens
Manually annotated by BRENDA team
Hagiya, Y.; Adachi, T.; Ogura, S.; An, R.; Tamura, A.; Nakagawa, H.; Okura, I.; Mochizuki, T.; Ishikawa, T.
Nrf2-dependent induction of human ABC transporter ABCG2 and heme oxygenase-1 in HepG2 cells by photoactivation of porphyrins: biochemical implications for cancer cell response to photodynamic therapy
J. Exp. Ther. Oncol.
7
153-167
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Lee, S.; Li, R.; Kim, B.; Palvolgyi, R.; Ho, T.; Yang, Q.Z.; Xu, J.; Szeto, W.L.; Honda, H.; Berliner, J.A.
Ox-PAPC activation of plasma membrane electron transport (PMET) system increases expression of heme oxygenase 1 (HO-1) in human aortic endothelial cell (HAEC)
J. Lipid Res.
50
265-274
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Kivelae, A.M.; Kansanen, E.; Jyrkkaenen, H.K.; Nurmi, T.; Ylae-Herttuala, S.; Levonen, A.L.
Enterolactone induces heme oxygenase-1 expression through nuclear factor-E2-related factor 2 activation in endothelial cells
J. Nutr.
138
1263-1268
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Chung, H.T.; Choi, B.M.; Kwon, Y.G.; Kim, Y.M.
Interactive relations between nitric oxide (NO) and carbon monoxide (CO): heme oxygenase-1/CO pathway is a key modulator in NO-mediated antiapoptosis and anti-inflammation
Methods Enzymol.
441
329-338
2008
Homo sapiens (P09601)
Manually annotated by BRENDA team
Lin, C.W.; Shen, S.C.; Hou, W.C.; Yang, L.Y.; Chen, Y.C.
Heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9
Mol. Cancer Ther.
7
1195-1206
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Hartung, R.; Parapuram, S.K.; Ganti, R.; Hunt, D.M.; Chalam, K.V.; Hunt, R.C.
Vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-beta and reactive oxygen species generation in human retinal pigment epithelial cells
Mol. Vis.
13
66-78
2007
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Reichard, J.F.; Motz, G.T.; Puga, A.
Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1
Nucleic Acids Res.
35
7074-7086
2007
Homo sapiens (P09601)
Manually annotated by BRENDA team
Chow, J.M.; Huang, G.C.; Lin, H.Y.; Shen, S.C.; Yang, L.Y.; Chen, Y.C.
Cytotoxic effects of metal protoporphyrins in glioblastoma cells: roles of albumin, reactive oxygen species, and heme oxygenase-1
Toxicol. Lett.
177
97-107
2008
Rattus norvegicus (P06762), Homo sapiens (P09601)
Manually annotated by BRENDA team
Huber III, W.; Backes, W.
Quantitation of heme oxygenase 1: Heme titration increases yield of purified protein
Anal. Biochem.
373
167-169
2008
Homo sapiens
Manually annotated by BRENDA team
Abdel Aziz, M.T.; Mostafa, T.; Roshdy, N.; Hosni, H.; Rashed, L.; Sabry, D.; Abdel Nasser, T.; Abdel Azim, O.; Abdel Gawad, O.
Heme oxygenase enzyme activity in human seminal plasma of fertile and infertile males
Andrologia
40
292-297
2008
Homo sapiens
Manually annotated by BRENDA team
Peng, D.; Ogura, H.; Zhu, W.; Ma, L.H.; Evans, J.P.; Ortiz de Montellano, P.R.; La Mar, G.N.
Coupling of the distal hydrogen bond network to the exogenous ligand in substrate-bound, resting state human heme oxygenase
Biochemistry
48
11231-11242
2009
Homo sapiens
Manually annotated by BRENDA team
Ogura, H.; Evans, J.P.; Peng, D.; Satterlee, J.D.; Ortiz de Montellano, P.R.; La Mar, G.N.
The orbital ground state of the azide-substrate complex of human heme oxygenase is an indicator of distal H-bonding: implications for the enzyme mechanism
Biochemistry
48
3127-3137
2009
Homo sapiens
Manually annotated by BRENDA team
Badyal, S.K.; Eaton, G.; Mistry, S.; Pipirou, Z.; Basran, J.; Metcalfe, C.L.; Gumiero, A.; Handa, S.; Moody, P.C.; Raven, E.L.
Evidence for heme oxygenase activity in a heme peroxidase
Biochemistry
48
4738-4746
2009
Homo sapiens (P09601)
Manually annotated by BRENDA team
Evans, J.P.; Kandel, S.; Ortiz de Montellano, P.R.
Isocyanides inhibit human heme oxygenases at the verdoheme stage
Biochemistry
48
8920-8928
2009
Candida albicans, Homo sapiens
Manually annotated by BRENDA team
Huber, W.J.; Marohnic, C.C.; Peters, M.; Alam, J.; Reed, J.R.; Masters, B.S.; Backes, W.L.
Measurement of membrane-bound human heme oxygenase-1 activity using a chemically defined assay system
Drug Metab. Dispos.
37
857-864
2009
Homo sapiens
Manually annotated by BRENDA team
Bilban, M.; Haslinger, P.; Prast, J.; Klinglmueller, F.; Woelfel, T.; Haider, S.; Sachs, A.; Otterbein, L.E.; Desoye, G.; Hiden, U.; Wagner, O.; Knoefler, M.
Identification of novel trophoblast invasion-related genes: heme oxygenase-1 controls motility via peroxisome proliferator-activated receptor gamma
Endocrinology
150
1000-1013
2009
Homo sapiens
Manually annotated by BRENDA team
Zhou, W.P.; Zhong, W.W.; Zhang, X.H.; Ding, J.P.; Zhang, Z.L.; Xia, Z.W.
Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1
Int. J. Mol. Med.
23
379-387
2009
Homo sapiens
Manually annotated by BRENDA team
Nakao, A.; Kaczorowski, D.J.; Sugimoto, R.; Billiar, T.R.; McCurry, K.R.
Application of heme oxygenase-1, carbon monoxide and biliverdin for the prevention of intestinal ischemia/reperfusion injury
J. Clin. Biochem. Nutr.
42
78-88
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Andersen, M.H.; Sorensen, R.B.; Brimnes, M.K.; Svane, I.M.; Becker, J.C.; thor Straten, P.
Identification of heme oxygenase-1-specific regulatory CD8+ T cells in cancer patients
J. Clin. Invest.
119
2245-2256
2009
Homo sapiens
Manually annotated by BRENDA team
Rahman, M.N.; Vlahakis, J.Z.; Roman, G.; Vukomanovic, D.; Szarek, W.A.; Nakatsu, K.; Jia, Z.
Structural characterization of human heme oxygenase-1 in complex with azole-based inhibitors
J. Inorg. Biochem.
104
324-330
2010
Rattus norvegicus (P06762), Rattus norvegicus (P23711), Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Rahman, M.N.; Vlahakis, J.Z.; Szarek, W.A.; Nakatsu, K.; Jia, Z.
X-ray crystal structure of human heme oxygenase-1 in complex with 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone: a common binding mode for imidazole-based heme oxygenase-1 inhibitors
J. Med. Chem.
51
5943-5952
2008
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Weis, N.; Weigert, A.; von Knethen, A.; Bruene, B.
Heme oxygenase-1 contributes to an alternative macrophage activation profile induced by apoptotic cell supernatants
Mol. Biol. Cell
20
1280-1288
2009
Homo sapiens
Manually annotated by BRENDA team
Ishikado, A.; Nishio, Y.; Morino, K.; Ugi, S.; Kondo, H.; Makino, T.; Kashiwagi, A.; Maegawa, H.
Low concentration of 4-hydroxy hexenal increases heme oxygenase-1 expression through activation of Nrf2 and antioxidative activity in vascular endothelial cells
Biochem. Biophys. Res. Commun.
402
99-104
2010
Homo sapiens
Manually annotated by BRENDA team
Park, S.Y.; Kim, Y.H.; Kim, E.K.; Ryu, E.Y.; Lee, S.J.
Heme oxygenase-1 signals are involved in preferential inhibition of pro-inflammatory cytokine release by surfactin in cells activated with Porphyromonas gingivalis lipopolysaccharide
Chem. Biol. Interact.
188
437-445
2010
Homo sapiens
Manually annotated by BRENDA team
Matsui, T.; Iwasaki, M.; Sugiyama, R.; Unno, M.; Ikeda-Saito, M.
Dioxygen activation for the self-degradation of heme: reaction mechanism and regulation of heme oxygenase
Inorg. Chem.
49
3602-3609
2010
Corynebacterium diphtheriae, Homo sapiens, Rattus norvegicus (P06762)
Manually annotated by BRENDA team
Lin, H.H.; Lai, S.C.; Chau, L.Y.
Heme oxygenase-1/carbon monoxide induces vascular endothelial growth factor expression via p38 kinase-dependent activation of Sp1
J. Biol. Chem.
286
3829-3838
2011
Homo sapiens
Manually annotated by BRENDA team
Gardner, J.D.; Yi, L.; Ragsdale, S.W.; Brunold, T.C.
Spectroscopic insights into axial ligation and active-site H-bonding in substrate-bound human heme oxygenase-2
J. Biol. Inorg. Chem.
15
1117-1127
2010
Homo sapiens
Manually annotated by BRENDA team
Sorrenti, V.; Guccione, S.; Di Giacomo, C.; Modica, M.N.; Pittala, V.; Acquaviva, R.; Basile, L.; Pappalardo, M.; Salerno, L.
Evaluation of imidazole-based compounds as heme oxygenase-1 inhibitors
Chem. Biol. Drug Des.
80
876-886
2012
Rattus norvegicus (P06762), Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Unno, M.; Matsui, T.; Ikeda-Saito, M.
Crystallographic studies of heme oxygenase complexed with an unstable reaction intermediate, verdoheme
J. Inorg. Biochem.
113
102-109
2012
Rattus norvegicus (P06762), Homo sapiens (P09601), Corynebacterium diphtheriae (Q54AI1)
Manually annotated by BRENDA team
Rahman, M.N.; Vukomanovic, D.; Vlahakis, J.Z.; Szarek, W.A.; Nakatsu, K.; Jia, Z.
Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds
J. R. Soc. Interface
10
20120697
2013
Homo sapiens (P09601), Homo sapiens (P30519), Homo sapiens
Manually annotated by BRENDA team
Rousset, F.; Nguyen, M.V.; Grange, L.; Morel, F.; Lardy, B.
Heme oxygenase-1 regulates matrix metalloproteinase MMP-1 secretion and chondrocyte cell death via Nox4 NADPH oxidase activity in chondrocytes
PLoS ONE
8
e66478
2013
Homo sapiens (P09601), Homo sapiens
Manually annotated by BRENDA team
Lee, P.J.; Shin, I.; Seo, S.Y.; Kim, H.; Kim, H.P.
Upregulation of both heme oxygenase-1 and ATPase inhibitory factor 1 renders tumoricidal activity by synthetic flavonoids via depleting cellular ATP
Bioorg. Med. Chem. Lett.
24
4845-4849
2014
Homo sapiens
Manually annotated by BRENDA team
Dorresteijn, M.J.; Paine, A.; Zilian, E.; Fenten, M.G.; Frenzel, E.; Janciauskiene, S.; Figueiredo, C.; Eiz-Vesper, B.; Blasczyk, R.; Dekker, D.; Pennings, B.; Scharstuhl, A.; Smits, P.; Larmann, J.; Theilmeier, G.; van der Hoeven, J.G.; Wagener, F.A.; Pickkers, P.; Immenschuh, S.
Cell-type-specific downregulation of heme oxygenase-1 by lipopolysaccharide via Bach1 in primary human mononuclear cells
Free Radic. Biol. Med.
78
224-232
2015
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Wang, S.; Hannafon, B.N.; Wolf, R.F.; Zhou, J.; Avery, J.E.; Wu, J.; Lind, S.E.; Ding, W.Q.
Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation
J. Nutr. Biochem.
25
515-525
2014
Homo sapiens
Manually annotated by BRENDA team
Andrade, B.B.; Pavan Kumar, N.; Mayer-Barber, K.D.; Barber, D.L.; Sridhar, R.; Rekha, V.V.; Jawahar, M.S.; Nutman, T.B.; Sher, A.; Babu, S.
Plasma heme oxygenase-1 levels distinguish latent or successfully treated human tuberculosis from active disease
PLoS ONE
8
e62618
2013
Homo sapiens
Manually annotated by BRENDA team
Spencer, A.L.; Bagai, I.; Becker, D.F.; Zuiderweg, E.R.; Ragsdale, S.W.
Protein/protein interactions in the mammalian heme degradation pathway heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase
J. Biol. Chem.
289
29836-29858
2014
Homo sapiens (P09601), Homo sapiens (P30519)
Manually annotated by BRENDA team
Barone, E.; Di Domenico, F.; Mancuso, C.; Butterfield, D.
The Janus face of the heme oxygenase/biliverdin reductase system in Alzheimer disease Its time for reconciliation
Neurobiol. Dis.
62
144-159
2014
Homo sapiens
Manually annotated by BRENDA team
Sigala, P.A.; Morante, K.; Tsumoto, K.; Caaveiro, J.M.; Goldberg, D.E.
In-cell enzymology to probe His-heme ligation in heme oxygenase catalysis
Biochemistry
55
4836-4849
2016
Homo sapiens (P09601), Homo sapiens, Synechocystis sp. PCC 6803 (P72849)
Manually annotated by BRENDA team
Davydov, R.; Fleischhacker, A.S.; Bagai, I.; Hoffman, B.M.; Ragsdale, S.W.
Comparison of the mechanisms of heme hydroxylation by heme oxygenases-1 and -2 Kinetic and cryoreduction studies
Biochemistry
55
62-68
2016
Homo sapiens (P30519), Homo sapiens
Manually annotated by BRENDA team
Hettiarachchi, N.; Dallas, M.; Al-Owais, M.; Griffiths, H.; Hooper, N.; Scragg, J.; Boyle, J.; Peers, C.
Heme oxygenase-1 protects against Alzheimers amyloid-beta(1-42)-induced toxicity via carbon monoxide production
Cell Death Dis.
5
e1569
2014
Rattus norvegicus (P06762), Homo sapiens (P09601)
Manually annotated by BRENDA team
Tseng, C.K.; Lin, C.K.; Wu, Y.H.; Chen, Y.H.; Chen, W.C.; Young, K.C.; Lee, J.C.
Human heme oxygenase 1 is a potential host cell factor against dengue virus replication
Sci. Rep.
6
32176
2016
Homo sapiens (Q96DI8), Homo sapiens
Manually annotated by BRENDA team