Information on EC 1.14.99.3 - heme oxygenase (biliverdin-producing)

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

EC NUMBER
COMMENTARY
1.14.99.3
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RECOMMENDED NAME
GeneOntology No.
heme oxygenase (biliverdin-producing)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
mechanism
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
a ferric hydroperoxide species must be an active intermediate in the first oxygenation step
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
determination of single turnover rate constants and reaction intermediates for heme oxygenase-1
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
hydroperoxoferri-heme oxygenase-1 is the reactive species directly forming the alpha-meso-hydroxyheme product by attack of the distal OH of the hydroperoxo moiety at the heme alpha-carbon
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
binding of heme stabilizes the solvent H-bonded network in the active site required for proper catalysis
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
docking model of heme and ferredoxin, indirect electron transfer from an iron-sulfur cluster in ferredoxin to the heme iron
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
electrophilic oxidation mechanism, stereochemical control of the reaction regiospecificity
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
model of activation mechanism of Fe-OOH
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
model of active site
-
protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
opened conformation of the heme pocket facilitates sequential product release, first iron, then biliverdin, iron triggers slow dissociation of biliverdin
P06762
protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
rate-limiting step of reaction is biliverdin release
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
rate-limiting step of reaction is release of product, involvement of phytochrome BphP in product release
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
selective oxygenation at the alpha-meso carbon, model of active site
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
a three-step mechanism, mechanism of the the third step, heme oxygenase enzymatic ring-opening mechanism of verdoheme, a process which maintains iron homeostasis, overview. Reaction mechanism for the FeOOH pathway and the FeHOOH pathway, and complete triplet-state mechanism, overview
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
heme degradation by heme oxygenase proceeds through three successive steps of O2 activation. The first step is formation of alpha-meso-hydroxyheme from from heme, second formation of verdoheme from alpha-meso-hydroxyheme, the third step is the ring opening of alpha-verdoheme to alpha-biliverdin, overview
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protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
heme degradation by heme oxygenase proceeds through three successive steps of O2 activation. The first step is formation of alpha-meso-hydroxyheme from heme, second formation of verdoheme from alpha-meso-hydroxyheme, the third step is the ring opening of verdoheme. Only alpha-verdoheme with the O atom in its alpha position, and not beta-, gamma-, or delta-verdoheme, is converted to biliverdin. The third step, like the first, shows regiospecificity, the distal Asp plays an important role in this step, similar to the first. The substrate heme is sandwiched between two helices, termed the proximal and distal helices. Reaction mechanism, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
heme degradation
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heme metabolism
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phycocyanobilin biosynthesis
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phycoerythrobilin biosynthesis I
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phycoerythrobilin biosynthesis II
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phycourobilin biosynthesis
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phycoviolobilin biosynthesis
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phytochromobilin biosynthesis
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Porphyrin and chlorophyll metabolism
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SYSTEMATIC NAME
IUBMB Comments
heme,hydrogen-donor:oxygen oxidoreductase (alpha-methene-oxidizing, hydroxylating)
Requires NAD(P)H and EC 1.6.2.4, NADPH---hemoprotein reductase. 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 central iron is kept in the reduced state by NAD(P)H.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
haem oxygenase
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ORP33 proteins
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-
-
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oxygenase, heme (decyclizing)
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proteins, specific or class, ORP33 (oxygen-regulated protein 33,000-mol.-wt.)
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CAS REGISTRY NUMBER
COMMENTARY
9059-22-7
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
two types of isoforms: an inducible heme oxygenase-1, HO1, and a constitutive heme oxygenase-2/3, HO2/3
UniProt
Manually annotated by BRENDA team
gene chuZ
UniProt
Manually annotated by BRENDA team
guinea pig
-
-
Manually annotated by BRENDA team
heme oxygenase is induced by light and delta-aminolevulinic acid, induction is inhibited by D-glucose
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-
Manually annotated by BRENDA team
strain O157:H7
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-
Manually annotated by BRENDA team
fragment
TrEMBL
Manually annotated by BRENDA team
constitutive isozyme HO-2
UniProt
Manually annotated by BRENDA team
gene HMOX1
UniProt
Manually annotated by BRENDA team
gene ho-1
-
-
Manually annotated by BRENDA team
inducible isozyme HO-1
UniProt
Manually annotated by BRENDA team
isoforms HO-1 and HO-2
-
-
Manually annotated by BRENDA team
isozyme HO-1
-
-
Manually annotated by BRENDA team
isozyme HO-1
UniProt
Manually annotated by BRENDA team
isozyme HO-1, an inducible heat-shock protein
UniProt
Manually annotated by BRENDA team
two isoforms, an inducible HO-1 and a constitutive HO-2
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-
Manually annotated by BRENDA team
heme oxygenase-1 is identical to the major 32000 Da mammalian stress-protein inducible by heat shock, H2O2, ultraviolet-A radiation, NaAsO2, pro-inflammatory cytokines, bacterial endotoxins, growth factors, NO, and tumor promotors, heme oxygenase-1 confers protection against oxidative stress
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-
Manually annotated by BRENDA team
C3H/HeN mice
UniProt
Manually annotated by BRENDA team
C57BL/6 mice
UniProt
Manually annotated by BRENDA team
constitutive isozyme HO-2
UniProt
Manually annotated by BRENDA team
female BALB/c and C57Bl/6 mice
UniProt
Manually annotated by BRENDA team
fetal B6129 mice
-
-
Manually annotated by BRENDA team
ICR, CD-1, mice
UniProt
Manually annotated by BRENDA team
inducible HO-1 isozyme and constitutive HO-2 isozyme
-
-
Manually annotated by BRENDA team
isozyme HO-1, an inducible heat-shock protein
UniProt
Manually annotated by BRENDA team
male BALB/c mice
UniProt
Manually annotated by BRENDA team
retired Swiss-Webster breeder mice
UniProt
Manually annotated by BRENDA team
Mus musculus C3H/HEN
C3H/HeN mice
UniProt
Manually annotated by BRENDA team
Mus musculus C57/BL/6
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-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
C57BL/6 mice
UniProt
Manually annotated by BRENDA team
pathogenic bacteria
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-
Manually annotated by BRENDA team
2 isoforms: heme oxygenase-1, inducible, heme oxygenase-2, constitutive
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-
Manually annotated by BRENDA team
BphO; gene bphO
UniProt
Manually annotated by BRENDA team
gene hemO; two genes pigA encoding PigA homologues
UniProt
Manually annotated by BRENDA team
PigA; gene pigA
UniProt
Manually annotated by BRENDA team
Pseudomonas aeruginosa KT24400
gene hemO; two genes pigA encoding PigA homologues
UniProt
Manually annotated by BRENDA team
BphO; gene bphO
UniProt
Manually annotated by BRENDA team
PigA; gene pigA
UniProt
Manually annotated by BRENDA team
Pseudomonas fluorescens Pf-5
BphO; gene bphO
UniProt
Manually annotated by BRENDA team
Pseudomonas fluorescens Pf-5
PigA; gene pigA
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
Pseudomonas putida KT24400
two genes pigA encoding PigA homologues
UniProt
Manually annotated by BRENDA team
BphO; pv. tomato, gene bphO
UniProt
Manually annotated by BRENDA team
PigA; pv. tomato, gene pigA
UniProt
Manually annotated by BRENDA team
Pseudomonas syringae DC3000
BphO; pv. tomato, gene bphO
UniProt
Manually annotated by BRENDA team
Pseudomonas syringae DC3000
PigA; pv. tomato, gene pigA
UniProt
Manually annotated by BRENDA team
2 isoforms: heme oxygenase-1, inducible; heme oxygenase-2, constitutive
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-
Manually annotated by BRENDA team
2 isoforms: heme oxygenase-1, inducible; heme oxygenase-2, constitutive; only minute amounts of heme oxygenase-1 in testis
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-
Manually annotated by BRENDA team
2 isoforms: heme oxygenase-1, inducible; heme oxygenase-2, constitutive; spleen heme oxygenase-1 is not induced by hematin
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-
Manually annotated by BRENDA team
; constitutive isozyme HO-2; inducible isozyme HO-1
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-
Manually annotated by BRENDA team
female and male Sprague Dawley rats
UniProt
Manually annotated by BRENDA team
heme oxygenase-1 is a heat shock protein that is inducible by numerous stimuli, including heavy metals, oxidative stress and injury, and cytokines, a 3 isomer, heme oxygenase-3, exhibits 90% homology to heme oxygenase-2, its mRNA has been detected in several tissues including kidney
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-
Manually annotated by BRENDA team
inducible isozyme HO-1, constitutive isozyme HO-2
UniProt
Manually annotated by BRENDA team
isozyme HO-1
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-
Manually annotated by BRENDA team
isozyme HO-1
UniProt
Manually annotated by BRENDA team
isozyme HO2
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-
Manually annotated by BRENDA team
male Sprague Dawley rats
UniProt
Manually annotated by BRENDA team
male sprague-dawley rats
UniProt
Manually annotated by BRENDA team
male sprague-dawley rats
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-
Manually annotated by BRENDA team
male Sprague-Dawley rats, inducible isozyme HO-1
UniProt
Manually annotated by BRENDA team
male Wistar rats
UniProt
Manually annotated by BRENDA team
male Wistar rats
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-
Manually annotated by BRENDA team
streptozotocin-induced diabetic rats
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-
Manually annotated by BRENDA team
truncated, soluble form
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-
Manually annotated by BRENDA team
two isoforms, an inducible HO-1 and a constitutive HO-2
UniProt
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
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-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
inducible isozyme HO-1, constitutive isozyme HO-2
UniProt
Manually annotated by BRENDA team
enzyme induction by curcumin is dramatically reduced by decreasing the temperature from 37C to 10C, cells pretreated with curcumin at 37C or during a programmed decrease in temperature exhibit increased resistance to oxidative stress-mediated injury
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-
Manually annotated by BRENDA team
strain PCC 6803, isozyme Syn HO-1
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Manually annotated by BRENDA team
strain PCC 6803, isozyme Syn HO-2
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
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bacterial HmuO and mammalian heme oxygenases are similar in their reaction mechanisms and structures
evolution
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HmuO and mammalian heme oxygenases are similar in their reaction mechanisms and structures
evolution
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas aeruginosa PAO1, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
evolution
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas fluorescence Pf-5, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
evolution
A4Y0Y8
Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas mendocina YMP, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
evolution
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas syringae DC3000, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
evolution
O69002, Q88P48, Q9HWR4
Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. Only one of the two PigA homologues identified in Pseudomonas putida KT2440 is encoded in an iron-associated gene cluster
evolution
Q88JR7
Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. Only one of the two PigA homologues identified in Pseudomonas putida KT2440 is encoded in an iron-associated gene cluster
evolution
Pseudomonas fluorescens Pf-5
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas fluorescence Pf-5, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
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evolution
Pseudomonas syringae DC3000
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas syringae DC3000, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
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evolution
Pseudomonas putida KT24400
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. Only one of the two PigA homologues identified in Pseudomonas putida KT2440 is encoded in an iron-associated gene cluster
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evolution
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. In Pseudomonas mendocina YMP, PigA is encoded in a cluster together with proteins involved in iron utilization while BphO is functionally and genetically coupled to the phytochrome BphP
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evolution
Pseudomonas aeruginosa KT24400
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Pseudomonas strains exhibit four possible enzyme compositions: (I) BphO, (II) PigA, (III) BphO and PigA and (IV) two PigAs. Only one of the two PigA homologues identified in Pseudomonas putida KT2440 is encoded in an iron-associated gene cluster
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malfunction
Q5HSH8
mutation of ChuZ abolishes the ability of Campylobacter jejuni to use hemin or hemoglobin as sources of iron
physiological function
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because HO-1 and NADPH-cytochrome P450 reductase (CPR) are membrane-bound proteins, the presence of membrane hydrophobic milieu (dilauroylphosphatidylcholine or endoplasmic reticulum membrane) may alter the mechanism by which cytosolic biliverdin reductase metabolizes its substrate biliverdin to bilirubin
physiological function
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HO enzyme activity in the human seminal plasma is related to spermatogenesis and sperm-motility processes
physiological function
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HO-1 is a negative regulator of trophoblast motility acting via up-regulation of peroxisome proliferator activated receptor (PPAR) gamma. In wound healing assays, trophoblast migration into the denuded area is diminished upon induction of HO-1
physiological function
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HO-1 is critically involved in macrophage polarization toward an M2 phenotype. HO-1 affects anti-inflammatory and antiapoptotic pathways in macrophages
physiological function
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HO-1-specific T cells isolated from the peripheral blood of cancer patients inhibit cytokine release, proliferation, and cytotoxicity of other immune cells
physiological function
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human patient wiht HO-1-deficiency died in his childhood with clinical manifestations, including growth failure, anemia, tissue iron deposition, lymphoadenopathy, leukocytosis and increased sensitivity to oxidative injury. HO-1 serves to provide cytoprotection against oxidative stress and is necessary in mammals
physiological function
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inducible form of HO-1, biliverdin, and CO possess generalized endogenous anti-inflammatory activities and provide protection against intestinal ischemia/reperfusion injury. Exogenous HO-1 expression, as well as exogenously administered CO and biliverdin, have potent cytoprotective effects on intestinal ischemia/reperfusion injury as well
physiological function
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mice lacking the HO-1 gene frequently die in utero, and the mice that survive to adulthood exhibit growth failure, anemia, chronic inflammation characterized by hepatosplenomegaly, leukocytosis, glomerulonephritis, and histological hepatoportal cellular infiltration. HO-1 serves to provide cytoprotection against oxidative stress and is necessary in mammals
physiological function
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4-hydroxy hexenal stimulates expression of the antioxidant enzyme HO-1 through the activation of Nrf2 in vascular endothelial cells resulting in prevention of oxidative stress-induced cytotoxicity, this may represent a possible mechanism to partly explain the cardioprotective effects of n-3 polyunsaturated fatty acids
physiological function
H8XZ68
BrHO1 may play an important role in abiotic stress tolerance of Chinese cabbage. Heme oxygenase is a regulatory enzyme that cleaves heme to biliverdin IXalpha, with the concomitant release of carbon monoxide and the production of free Fe2+
physiological function
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by catalyzing the first step in heme degradation, heme oxygenase plays a vital role in maintaining proper heme homeostasis. Isozymes HO-1 and HO-2, exist that catalyze the same reaction but differ in several notable ways, overview
physiological function
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heme oxygenase-1 signals are involved in preferential inhibition of pro-inflammatory cytokine release by surfactin, produced by Bacillus subtilis, in cells activated with Porphyromonas gingivalis lipopolysaccharide
physiological function
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heme oxygenase-1/CO induces vascular endothelial growth factor expression via p38 kinase-dependent activation of Sp1. CO-induced VEGF promoter activation requires the binding of the Sp1 transcriptional factor to a cis-regulatory sequence located at the VEGF promoter. HO-1/CO induced p38-dependent phosphorylation of Sp1 at Thr453 and Thr739 both in vitro and in vivo
physiological function
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heme oxygenases are widely distributed enzymes involved in the oxidative cleavage of the heme macrocycle that yields the open-chain tetrapyrrole biliverdin IX, CO, and iron
physiological function
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HO-1 together with dichloromethane induces interleukin-10 expression in liver. HO-1, acting through the Nfe2l2, i.e. Nrf2, transcription factor, links anti-inflammatory cytokine expression to activation of mitochondrial biogenesis. HO1 induction after LPS stimulates anti-inflammatory interleukin-10 and interleukin-1 receptor antagonist expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-alpha expression
physiological function
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HugZ is part of the iron acquisition mechanism of Helicobacter pylori, and is required for the adaptive colonization of the pathogen in human hosts. Arg166, which is involved in azide binding, is essential for HugZ enzymatic activity, whereas His245 is not, implying that HugZ has an enzymatic mechanism distinct from other heme oxygenases
physiological function
D9IWR7
MsHO1 may play an important role in oxidative responses
physiological function
P09601
heme oxygenase has cytoprotective properties and may play a role in several disease states. HO-1 activity is upregulated in response to several therapeutic treatments and is implicated in promoting tumour growth. HO-1-derived CO is associated with angiogenesis, inducing vascular endothelial growth factor synthesis, and stimulating the proliferation of endothelial cells. Role of the HO/CO system in neuronal complications, particularly of HO-1, heme oxygenase has cytoprotective properties and may play a role in several disease states. Role of the HO/CO system in neuronal complications, particularly of HO-1
physiological function
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heme oxygenase-1 is the limiting enzyme in heme catabolism. Induction of HO-1 expression decreases dramatically NADPH oxidase Nox4 activity in C-20/A4 and HEK-293T-RExTM Nox4 cell lines, mediated by carbon monoxide, the decrease is not accompanied by any change in the expression, the subcellular localization or the maturation of Nox4. Inhibition of the heme synthesis by succinylacetone rather than heme catabolism by HO-1, leads to a confinement of the Nox4/p22phox heterodimer in the endoplasmic reticulum with an absence of redox differential spectrum highlighting an incomplete maturation. HO-1 decreases MMP-1 expression and chondrocytes DNA fragmentation via CO release
physiological function
O69002, Q88P48, Q9HWR4
role of PigA in iron acquisition
physiological function
Q88JR7
role of PigA in iron acquisition
physiological function
O69002, Q88P48, Q9HWR4
role of PigA in iron acquisition, in strains containing no PigA, this function may be fulfilled by BphO
physiological function
Q4K657, Q4K7S1
role of PigA in iron acquisition, in strains containing no PigA, this function may be fulfilled by BphO
physiological function
A4Y0Y8
role of PigA in iron acquisition, in strains containing no PigA, this function may be fulfilled by BphO
physiological function
Q885D4, Q887K9
role of PigA in iron acquisition, in strains containing no PigA, this function may be fulfilled by BphO
physiological function
Q5HSH8
the enzyme enables the organism to use heme as the sole iron source
physiological function
Pseudomonas fluorescens Pf-5, Pseudomonas syringae DC3000
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role of PigA in iron acquisition, in strains containing no PigA, this function may be fulfilled by BphO
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physiological function
Pseudomonas putida KT24400
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role of PigA in iron acquisition
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physiological function
Mus musculus C57/BL/6
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HO-1 together with dichloromethane induces interleukin-10 expression in liver. HO-1, acting through the Nfe2l2, i.e. Nrf2, transcription factor, links anti-inflammatory cytokine expression to activation of mitochondrial biogenesis. HO1 induction after LPS stimulates anti-inflammatory interleukin-10 and interleukin-1 receptor antagonist expression in mouse liver, human HepG2 cells, and mouse J774.1 macrophages but blunted tumor necrosis factor-alpha expression
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physiological function
-
role of PigA in iron acquisition, in strains containing no PigA, this function may be fulfilled by BphO
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physiological function
Pseudomonas aeruginosa KT24400
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role of PigA in iron acquisition
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malfunction
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mutation of the distal Asp decreases the verdoheme ring opening activity
additional information
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in cells, Hmox1 or Nfe2l2 RNA silencing prevents IL-10 and IL-1Ra up-regulation, and HO-1 induction fails post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2-/- mice
additional information
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modulation of HO catalysis by ligands targeting the critical distal pocket structure, overview
additional information
P06762
modulation of HO catalysis by ligands targeting the critical distal pocket structure, overview
additional information
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physiological effects of angiotensin II with and without tin mesoporphyrin on renal and aortic HO-1 activity, overview
additional information
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QM/MM calculations based on this crystal structure exploring the reaction mechanisms starting from the FeOOH-verdoheme and FeHOOH-verdoheme complexes, which mimic, respectively, the O2- and H2O2-supported degradations. The rate-determining step is the initial O-O bond breaking step, which is either homolytic, for FeHOOH-verdoheme, or coupled to electron and proton transfers, in FeOOH-verdoheme. The FeHOOH-verdoheme complex is more reactive than the FeOOH-verdoheme complex
additional information
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regulation of isozyme HO-2, overview. Presence of three Cys residues as part of heme-regulatory motifs in HO-2, low-spin Fe(III) heme species are characteristic of thiolate ligation is formed when Cys265 is reduced. Resonance Raman data collected at different temperatures reveal an intriguing temperature dependence of the iron spin state in the heme-HO-2 complex
additional information
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analysis of enzyme-protohemin substrate variant complexes and of enzyme-propionate substrate complexes by NMR, active site structure, overview. The enzyme's C-terminal fragment interacts with the active site of the enzyme. The C-terminal dipeptide Arg208-His209 cleaves spontaneously. Stronger hydrophobic contacts between pyrroles A and B with the enzyme contribute more substantially to the substrate binding free energy than in mammalian HOs, liberating one propionate to stabilize the C-terminus
additional information
Q5HSH8
heme is bound in its binding site on the dimer interface by four histidine side-chains through hydrophobic interactions, canonical heme-binding site structure, reaction mechanism and structure-function relationship, overview
additional information
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heme oxygenase is an enzyme that catalyzes the regiospecific conversion of heme to biliverdin IXalpha, carbon monoxide, and free Fe(II). Heme degradation by heme oxygenase proceeds through three successive steps of O2 activation. The first step is formation of alpha-meso-hydroxyheme from from heme, second formation of verdoheme from alpha-meso-hydroxyheme, the third step is the ring opening of verdoheme, Only alpha-verdoheme with the O atom in its alpha position, and not beta-, gamma-, or delta-verdoheme, is converted to biliverdin. The third step, like the first, shows regiospecificity, the distal Asp plays an important role in this step, similar to the first. The substrate heme is sandwiched between two helices, termed the proximal and distal helices
additional information
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heme oxygenase is an enzyme that catalyzes the regiospecific conversion of heme to biliverdin IXalpha, carbon monoxide, and free Fe(II). Heme degradation by heme oxygenase proceeds through three successive steps of O2 activation. The first step is formation of alpha-meso-hydroxyheme from heme, second formation of verdoheme from alpha-meso-hydroxyheme, the third step is the ring opening of verdoheme. Only alpha-verdoheme with the O atom in its alpha position, and not beta-, gamma-, or delta-verdoheme, is converted to biliverdin. The third step, like the first, shows regiospecificity, the distal Asp plays an important role in this step, similar to the first. The substrate heme is sandwiched between two helices, termed the proximal and distal helices
additional information
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structure-activity relationship analysis
additional information
-
the enzyme shows substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions. The enzyme's C-terminus interacts with substrate in solution, interaction of the C-terminus with the active site destabilizes the crystallographic protohemin orientation, which is consistent with optimizing the His207-Asp27 H-bond, active site stress for product release, NMR analysis of wild-type and mutant enzymes, overview. Thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl to methyl to hydrogen substitutions and with enzyme C-terminal deletions. Replacing bulky vinyls with hydrogens results in a 180 degree rotation of substrate about the alpha,gamma-meso axis in the active site
additional information
Rattus norvegicus Sprague-Dawley
-
physiological effects of angiotensin II with and without tin mesoporphyrin on renal and aortic HO-1 activity, overview
-
additional information
Mus musculus C57/BL/6
-
in cells, Hmox1 or Nfe2l2 RNA silencing prevents IL-10 and IL-1Ra up-regulation, and HO-1 induction fails post-LPS in Nfe2l2-silenced cells and post-sepsis in Nfe2l2-/- mice
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
15-phenylheme + electron donor + O2
10-phenylbiliverdin IXalpha + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
P09601
-
-
-
-
5-phenylheme + electron donor + O2
biliverdin IXalpha + Fe2+ + CO + oxidized eletron donor + H2O + benzoic acid
show the reaction diagram
P09601
-
-
-
-
alpha-meso-formylmesoheme + NADPH
? + NADP+
show the reaction diagram
-
exclusively oxidized at a non-formyl substituted meso-carbon
-
?
alpha-meso-hydroxyhemin IX + reduced acceptor + O2
verdoheme IXalpha + CO + acceptor + H2O
show the reaction diagram
-
-
-
-
?
beta-meso-hydroxyhemin IX + reduced acceptor + O2
verdoheme IXbeta + CO + acceptor + H2O
show the reaction diagram
-
-
-
-
?
delta-meso-hydroxyhemin IX + reduced acceptor + O2
verdoheme IXdelta + CO + acceptor + H2O
show the reaction diagram
-
-
-
-
?
gamma-CH-Fe(cor) + 3 AH2 + 3 O2
?
show the reaction diagram
-
the regioisomeric iron corrole is an artificial, not-natural substrate, the enzymatic cleavage happens selectively at the unexpected bipyrrolic position and yields a biomimetic biliverdin-like product. The enzymatic corrole ring opening is selective for this corrole regioisomer and for plant-type heme oxygenase, mechanism, overview
-
-
?
gamma-meso-hydroxyhemin IX + reduced acceptor + O2
verdoheme IXgamma + CO + acceptor + H2O
show the reaction diagram
-
-
-
-
?
heme + 2 NADH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NAD+ + H2O
show the reaction diagram
-
NADH-dependent heme degradation system may have a biological role in regulating the concentration of respiratory hemoproteins and the disposition of the aberrant forms of the mitochondrial hemoproteins
-
?
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
-
-
-
-
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
-
-
-
?
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
-
-
-
?
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + 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 + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
involved in heme metabolism
-
?
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 + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
P09601
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
P23711
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
D9IWR7
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q885D4, Q887K9
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q5HSH8
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
O69002, Q88P48, Q9HWR4
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q4K657, Q4K7S1
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
A4Y0Y8
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q88JR7
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
requires three oxidative reaction steps, via alpha-meso-hydroxy-heme and verdoheme, detailed overview
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
P06762
requires three oxidative reaction steps, via alpha-meso-hydroxy-heme and verdoheme, detailed overview
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
O69002, Q88P48, Q9HWR4
natural electron donor for PigA from Pseudomonas aeruginosa PAO1 is ferredoxin-NADP+-oxidoreductase
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
reaction intermediate verdoheme and the verdoheme-enzyme complex are gradually degraded in the presence of O2
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q885D4, Q887K9
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
O69002, Q88P48, Q9HWR4
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q4K657, Q4K7S1
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
A4Y0Y8
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q88JR7
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
O69002, Q88P48, Q9HWR4
with NADPH, ferredoxin from spinach, and spinach ferredoxin-NADP+-oxidoreductase
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas fluorescens Pf-5
Q4K657, Q4K7S1
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas fluorescens Pf-5
Q4K657, Q4K7S1
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Rattus norvegicus Sprague-Dawley
P23711
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas syringae DC3000
Q885D4, Q887K9
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas syringae DC3000
Q885D4, Q887K9
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas putida KT24400
Q88JR7
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
A4Y0Y8
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas aeruginosa KT24400
Q88P48
with NADPH, ascorbate, FNR and ferredoxin as exogenous reductant system, spectroscopic determination
-
-
?
heme + 3 AH2 + 3 O2
biliverdin IXalpha + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin IXalpha + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
H8XZ68
-
-
-
?
heme + 3 reduced ascorbate + 3 O2
biliverdin + Fe2+ + CO + 3 oxidized ascorbate + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 reduced ascorbate + 3 O2
biliverdin + Fe2+ + CO + 3 oxidized ascorbate + 3 H2O
show the reaction diagram
Q5HSH8
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P09601, P30519
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
O70252, P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Q5E9F2
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
activation of the enzyme leads to induction of the ABC transporter ABCG2, but not of ABCB6
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
biliverdin is involved in hemin degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
CO plays a role in cGMP production, p38 mitogen-activated protein kinase activation, and nuclear factor-kB activation, as part of the heme oxygenase-1/carbon monoxide, HO-1/CO, system, overview, correlation of HO-1-mediated cytoprotection with a decrease in intracellular free iron amounts. Biliverdin is a third generated heme catabolite by HO-1 and is converted to bilirubin by the catalytic reaction of biliverdin reductase. Both compounds are reducing species and hence may play a role in the protective response to vascular injury by oxidative stress
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
endogenous HO-1 shows anti-apoptotic activity, and is overexpressed in various cancer diseases and might contribute to cancer progression
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
exogenous CO activates Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase, resulting in HO-1 expression, mechanism, overview, CO renders endothelial cells resistant to ER stress not only by downregulating C/EBP homologous protein expression via p38 mitogen-activated protein kinase activation but also by upregulating Nrf2-dependent HO-1 expression via PERK activation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P30519
first step in the heme degradation pathway
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heat shock factor 1, HSF1, is directly involved in the transcriptional regulation of ho-1 mediated by the enzyme's cadmium-responsive element, mechanism, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heme degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heme oxygenase is the rate-limiting enzyme in heme degradation to biliverdin, heme oxygenase-1 catalyzes the degradation of heme and forms antioxidant bile pigments as well as the signaling molecule carbon monoxide, HO-1 is inducible in response to a variety of chemical and physical stress conditions to function as a cytoprotective molecule. Catalytic inactive heme oxygenase-1 deletion mutant protein regulates its own expression in oxidative stress in a positive feedback manner, feed-forward autoregulation of HO-1 in oxidative stress, overview, HO-1 protein also plays a role in regulating cadmium chloride-mediated HO-1 gene induction
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heme oxygenase-1 is regulated by the Nrf2/anti-oxidant response element, ARE, pathway, which plays an important role in regulating cellular anti-oxidants
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO is a microsomal enzyme and catalyzes the oxidation of the alpha-meso-carbon bridge of heme moieties resulting in the generation of ferrous iron, carbon monoxide and biliverdin. HO-1 is inducible and plays a main role in the cellular oxidant/antioxidant balance, whereas HO-2 is constitutive and involved in the physiologicalmetabolism of heme
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
HO-1 acts as anti-oxidant and protects cells against injury, it regulates neutrophil O2- production and protects the intestine from damage following EtOH and burn injury, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 catalyzes the rate-limiting step of heme degradation and plays an important anti-inflammatory role via its enzymatic products carbon monoxide and biliverdin
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 exhibits cytoprotective function, enzyme induction, e.g. by dehydrocostus lactone, causes the nuclear accumulation of the nuclear factor E2-related factor 2, Nrf2, and increases the promoter activity of antioxidant response element, ARE, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 gene is a glia-expressing wound-responsive gene, HO-1 gene expression associated with traumatic brain injury involving the toll-like receptor 2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 induction in vivo inhibits cytokine production in synovial tissue, while HO-1 inhibition restores it, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is a cell-protective anti-oxidant enzyme, which is sensitively induced by oxidative stress and regulated by oxidized-1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphocholine, i.e. Ox-PAPC, and Nrf2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is a critical cell defence enzyme against oxidative stress, HO-1 participates in the protective effect afforded by neuronal nicotinic acetylcholine receptors, nAChR, activation, which activates the neuroprotective signaling cascade, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
HO-1 is a heat shock protein, and it provides endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is a key enzyme in the cellular response to tissue injury and oxidative stress. HO-1 enzymatic activity results in the formation of the cytoprotective metabolites CO and biliverdin
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is an antioxidant and cytoprotective enzyme. Methoxychalcones, especially 5-methoxychalcone, 3,4,5-trimethoxychalcone, and 3,4,5,3',4',5'-hexamethoxychalcone, induce the enzyme expression and activity in macrophages without causing cytotoxicity, they also cause anti-inflamatory affects, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
HO-1 is an inducible enzyme that catalyzes the rate-limiting step in the degradation of heme to biliverdin, CO and iron
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase, CPR, releasing free iron and carbon monoxide
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is the rate-limiting enzyme in heme degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 participates in the degradation of heme, the enzyme is involved in tumor development
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
HO-1 participates in the degradation of heme, the enzyme is involved in tumor development
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 shows anti-inflammatory effect, inhibition of HO-1 or scavenging of CO significantly reverses the inhibition of LPS-stimulated nitrite accumulation by tanshinone IIA, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
HO-1 shows anti-inflammatory properties
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 shows vasculoprotective and anti-inflammatory activity, it is ptionally regulated by peroxisome proliferator-activated receptors PPARalpha and PPARgamma in vascular cells, inhibition of HO-1 enzymatic activity reverses PPAR ligand-mediated inhibition of cell proliferation and expression of cyclooxygenase-2 in vascular smooth muscle cells, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 transcriptional regulation system, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
in aortic smooth muscle cells, induction of HO-1 confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 that is involved in negative regulation of cellular proliferation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
in vascular smooth muscle cells, induction of HO-1 confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 that is involved in negative regulation of cellular proliferation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Q5E9F2
induction of HO-1 leads to a reduction of superoxide and increases levels of spermine-NoNoate, HO-1 is involved in artery vascular relaxation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
induction of HO-1 via the ERK-Nrf2-ARE signaling pathway is involved in protecting cells from oxidative stress, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
inhibition or selective knockdown of HO-1 has anti-inflammatory effects via bilirubin, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P09601, P30519
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-1 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
O70252, P14901
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-1 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
O70252, P14901
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-2 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P09601, P30519
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-2 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
the enzyme has anti-inflammatory activity and is involved in mediation of curcumin's inhibitory effect on inducible NO synthase expression and NO production. Treatment with HO inhibitor abolishes the inhibitory effect of curcumin on lipopolysaccharide-induced NF-kappaB activation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
the enzyme plays a protective role against hypoxic injury, and in the vicious cycle of low-flow priapism
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
the enzyme shows anti-inflammatory activity, HO-1 expression is induced via the ERK1/2 activation pathway
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
the gene encoding HO-1 is a Nrf2-regulated gene. NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells, e.g. by H2O2 and 6-hydroxydopamine
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P30519
proper orientation of heme in HO-2 is required for the regioselective oxidation of the alpha-mesocarbon. This is accomplished by interactions within the heme binding pocket, which is made up of two helices. The iron coordinating residue, His45, resides on the proximal helix. The distal helix contains highly conserved glycine residues that allow the helix to flex and interact with the bound heme. Tyr154, Lys199, and Arg203 orient the heme through direct interactions with the heme propionates, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
the C-terminal 23 amino acids are essential for maximal catalytic activity
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Mus musculus C57BL/6
P14901
HO-1 shows anti-inflammatory properties
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Mus musculus C57BL/6
-
HO-1 gene is a glia-expressing wound-responsive gene, HO-1 gene expression associated with traumatic brain injury involving the toll-like receptor 2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Mus musculus C3H/HEN
P14901
endogenous HO-1 shows anti-apoptotic activity, and is overexpressed in various cancer diseases and might contribute to cancer progression
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
NADH can replace NADPH at concentrations higher than 5 mM in vitro, NADH is unlikely to be an electron donor in vivo
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
overview, substrate specificity
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADH
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADH
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADH
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
iron-protoporphyrin IX is the most active substrate, lower activity with: iron-mesoporphyrin IX, iron-deuteroheme IX, iron-coproheme I, alpha and beta chain of hemoglobin, poor substrates: oxyhemoglobin, carboxyhemoglobin, myoglobin
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
alpha-meso-oxyprotoheme is an intermediate of heme degradation that is converted stereospecifically into biliverdin IXa via verdoheme IXa
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
Ni, Mn, and Sn protoporphyrin IX is not oxidized, oxidation of Co-heme
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
synthetic hemins XIII and III and iron porphyrin are better substrates than the natural substrate hemin IX, 83 and 86% of hemin IX activity with mesohemin IX and hematohemin IX respectively
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
enzyme oxidizes protoheme, hematoheme, hematoheme dimethyl ester, dicysteinyl hematoheme, and heme undecapeptide, conversion of hematoheme to hematobilirubin requires the presence of: NADPH, NADPH-cytochrome c reductase, biliverdin reductase and O2
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
testis heme oxygenase 2 oxidizes Fe-protopophyrin, ferric hematoporphyrin acetate and ferric hematoporphyrin
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor ascorbic acid
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
algal heme oxygenase requires a second reductant in addition to reduced pyridine nucleotide
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH, reductase: human or E. coli NADPH-cytochrome P450 reductase or putidaredoxin/putidaredoxin reductase
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
NADH-dependent heme-degradation activity, 16% of NADH activity with 0.5 mM NADPH
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
enzyme catalyzes oxidative cleavage of both heme b and heme c
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
porphyrins without chelated iron and metalloporphyrins other than iron porphyrins are not oxidized
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
intact cytochrome c is not oxidized
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
cytochrome c and myoglobin are not oxidized
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
NADPH is more effective than NADH
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
NADPH is more effective than NADH
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH
-
-
-
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
electron donor NADPH
-
-
?
heme + electron donor + O2
biliverdin IXalpha + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
prefers ferredoxin or ascorbate as electron donor
-
-
?
heme + electron donor + O2
alpha-biliverdin + beta-biliverdin + delta-biliverdin + Fe2+ + CO + oxidized eletron donor + H2O
show the reaction diagram
-
-
wild-type, mutant N19K, mutant F117Y, 30% beta- and 70% delta-isomer, N19K/F117Y double mutant, 55% alpha-, 10% beta-, 35% delta-isoform
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized electron donor + 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 electron donor + 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 electron donor + H2O
show the reaction diagram
-
-
-
-
?
heme + electron donor + O2
biliverdin + Fe2+ + CO + oxidized electron donor + H2O
show the reaction diagram
P23711
-
-
-
?
heme + ferredoxin + O2
biliverdin IXalpha + Fe2+ + CO + A + H2O
show the reaction diagram
-
HY1, HO3, and HO4
-
-
?
heme + NADH + O2
biliverdin + Fe2+ + CO + NAD+ + H2O
show the reaction diagram
-
-
-
-
?
heme + NADH + O2
biliverdin + Fe2+ + CO + NAD+ + H2O
show the reaction diagram
-
-
-
-
?
heme + NADPH + O2
biliverdin IXalpha + Fe2+ + CO + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
heme + NADPH + O2
biliverdin IXalpha + Fe2+ + CO + NADP+ + H2O
show the reaction diagram
-
-
wild-type, selective production of biliverdin IXalpha
-
?
heme + NADPH + O2
biliverdin IXdelta + biliverdin IXalpha + Fe2+ + CO + NADP+ + H2O
show the reaction diagram
-
-
mutant R183E, yields about 20% of product biliverdin IXdelta
-
?
hemin + reduced acceptor + O2
alpha-meso-hydroxyhemin IX + CO + acceptor + H2O
show the reaction diagram
-
-
-
-
?
methemoglobin + electron donor + O2
?
show the reaction diagram
-
-
-
-
?
verdoheme IXalpha + H2O
biliverdin IXalpha + Fe2+
show the reaction diagram
-
-
-
-
-
methemoglobin + electron donor + O2
?
show the reaction diagram
-
30% of activity with heme
-
-
?
additional information
?
-
-
involved in the control of wound healing
-
-
-
additional information
?
-
-
reaction proceeds via three steps, first step is alpha-regioselective hydroxylation of hemin, second degradation of meso-hydroxyhemin to verdoheme and third degradation of verdoheme to biliverdin, which again is stereoselective for verdoheme IXalpha. In the second step, enzyme would convert all four isomers of meso-hydroxyhemin
-
-
-
additional information
?
-
P30519
structure-function analysis
-
-
-
additional information
?
-
P06762
butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries involving Nrf2 activation, overview
-
-
-
additional information
?
-
-
capsaicin induces heme oxygenase-1 expression in Hep-G2 cells via activation of PI3K-Nrf2 signaling, and capsaicin protects against SIN-1-induced cytotoxicity, which is abolished by HO-1 inhibition
-
-
-
additional information
?
-
P06762
expression and activity of heme oxygenase-1 is elevated in artificially induced low-flow priapism in rat penile tissues, overview
-
-
-
additional information
?
-
-
expression of Hepatitis C virus core protein sensitizes hepatocytes to toxic injury and inhibits the induction of HO-1 in response to stress, overview
-
-
-
additional information
?
-
-
heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9, overview
-
-
-
additional information
?
-
-
heme oxygenase-1/CO pathway is a key modulator in NO-mediated antiapoptosis and anti-inflammation, mechanisms, overview, mechanisms for the HO-1-mediated inhibition of NO production, activation of the PI3K/Akt pathway, overview
-
-
-
additional information
?
-
-
hemoglobin neurotoxicity is attenuated by inhibitors of the protein kinase CK2 and protein kinase C independent of heme oxygenase activity
-
-
-
additional information
?
-
-
HO-1 and its byproduct biliverdin play major roles in the pathophysiological cascade leading to renal I/R injury
-
-
-
additional information
?
-
P09601
HO-1 gene regulation system, dynamic roles of transcriptional repressor BACH1 and transcription factor NRF2 in the transcription of the heme oxygenase-1 gene, overview
-
-
-
additional information
?
-
-
HO-1 is involved in host defense reactions against various stresses, HO-1 modulates immunocyte activation and functions and suppresses mast cell degranulation, overview
-
-
-
additional information
?
-
-
HO-1 is involved in the function of bax inhibitor-1, BI-1, an anti-apoptotic protein that is located in endoplasmic reticulum membranes and protects cells from endoplasmic reticulum stress-induced apoptosis. For BI-1 associated function, HO-1 expression is induced by nuclear factor erythroid 2-related factor 2, overview
-
-
-
additional information
?
-
-
HO-1 protein delivery mediates activation of various transcription factors, nuclear localization of HO-1 has a signalling role, effect of nuclear localization of HO-1oncell viability, overview
-
-
-
additional information
?
-
-
HO-1 regulation, HO-1 autoregulation, and HO-1 regulatory functions, activation of MAPK pathways is not required in HO-1 self-regulation, overview
-
-
-
additional information
?
-
P14901
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
-
additional information
?
-
P06762
inhibition of heme oxygenase-1 protects against tissue injury in carbon tetrachloride exposed livers, SnPP-IX-mediated HO-1 inhibition markedly aggravates intrahepatic leukocyte-endothelial cell interaction with an almost 2fold increase of the number of adherent leukocytes when compared with solely CCl4-exposed livers, overview
-
-
-
additional information
?
-
P14901
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
-
additional information
?
-
-
NO derived from LPS-induced nitric oxide synthase, NOS, entails an increase in HO activity and this activity, in turn, is involved in the consequent inhibition of NOS, overview
-
-
-
additional information
?
-
P14901
overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
-
-
-
additional information
?
-
-
PMA-dependent activation of HO-1 is mediated via a nonclassical NF-kappaB pathway that is independent of IKK2 activity
-
-
-
additional information
?
-
-
the anti-inflammatory activity of Phellinus linteus is mediated through the PKCdelta/Nrf2/ARE signaling to up-regulation of heme oxygenase-1
-
-
-
additional information
?
-
-
the enzyme activity is positively correlated with nitric oxide and cGMP levels in cavernous tissue, overview
-
-
-
additional information
?
-
-
the enzyme has anti-inflammatory function in the vascular system via production of antioxidants bilirubin and biliverdin as well as CO, the enzyme contributes to cardiovascular health
-
-
-
additional information
?
-
-
the enzyme is involved in cancer cell response to photodynamic therapy, overview
-
-
-
additional information
?
-
-
ho-1 forms complexes with proteins from heavy metal-treated HeLa cells
-
-
-
additional information
?
-
-
screening for heme proteins with heme oxygenase activity after de novo synthesis of the heme proteins on a membrane-coupled template, overview
-
-
-
additional information
?
-
-
BphO, a heme oxygenase, produces the linear tetrapyrrole chromophore biliverdin IXa, potential protective role of the BphO reaction product biliverdin, overview
-
-
-
additional information
?
-
-
a pattern of substrate methyl contact shifts that places the lone iron pi-spin in the dxz orbital, rather than the dyz orbital found in the cyanide complex. Low-spin, (dxy)2(dyz,dxz)3, ground state in both azide and cyanide complexes. Switch from singly occupied dyz for the cyanide to dxz for the azide complex of HO is consistent with the orbital hole determined by the azide pi-plane in the latter complex, which is ca. 90 in-plane rotated from that of the imidazole pi-plane
-
-
-
additional information
?
-
-
ability of uncoupled HO-1 to produce large quantities of H2O2, H2O2 generation is much more efficient with the full-length form of HO-1 than with the soluble form
-
-
-
additional information
?
-
-
The first HO reaction step is the regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, the second is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. The third reaction step is a major rate-determining step of HO catalysis to regulate the enzyme activity. HO catalysis is unique in that all three O2 activations are performed by the substrate itself, analysis of structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps, overview. FeOOH verdoheme is the key intermediate of the ring-opening reaction, mechanism, overview. Critical functioning of the FeOOH species in HO heme self-oxidation and catalytic importance of the distal hydrogen bonding network in its unique O2 activation
-
-
-
additional information
?
-
-
The first HO reaction step is the regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, the second is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. The third reaction step is a major rate-determining step of HO catalysis to regulate the enzyme activity. HO catalysis is unique in that all three O2 activations are performed by the substrate itself, analysis of structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps, overview. FeOOH verdoheme is the key intermediate of the ring-opening reaction, mechanism, overview. Critical functioning of the FeOOH species in HO heme self-oxidation and catalytic importance of the distal hydrogenbonding network in its unique O2 activation
-
-
-
additional information
?
-
P06762
The first HO reaction step is the regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, the second is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. The third reaction step is a major rate-determining step of HO catalysis to regulate the enzyme activity. HO catalysis is unique in that all three O2 activations are performed by the substrate itself, analysis of structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps, overview. FeOOH verdoheme is the key intermediate of the ring-opening reaction, mecjanism, overview. Critical functioning of the FeOOH species in HO heme self-oxidation and catalytic importance of the distal hydrogenbonding network in its unique O2 activation
-
-
-
additional information
?
-
-
heme oxygenase activity in rat spleen and brain microsomal fractions is determined by the quantitation of CO formed from the degradation of methemalbumin, i.e. heme complexed with albumin
-
-
-
additional information
?
-
-
structure-function relationship and analysis, overview
-
-
-
additional information
?
-
P06762
structure-function relationship and analysis, overview
-
-
-
additional information
?
-
O69002, Q88P48, Q9HWR4
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
additional information
?
-
Q88JR7
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
additional information
?
-
Q885D4, Q887K9
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
O69002, Q88P48, Q9HWR4
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Q4K657, Q4K7S1
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
A4Y0Y8
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Pseudomonas fluorescens Pf-5
Q4K657, Q4K7S1
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Rattus norvegicus Sprague-Dawley
-
heme oxygenase activity in rat spleen and brain microsomal fractions is determined by the quantitation of CO formed from the degradation of methemalbumin, i.e. heme complexed with albumin
-
-
-
additional information
?
-
Pseudomonas syringae DC3000
Q885D4, Q887K9
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Mus musculus C57BL/6
P14901
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
-
additional information
?
-
Pseudomonas putida KT24400
Q88JR7
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
additional information
?
-
Mus musculus C3H/HEN
P14901
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
-
additional information
?
-
A4Y0Y8
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Pseudomonas aeruginosa KT24400
Q88P48
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
heme + 2 NADH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NAD+ + H2O
show the reaction diagram
-
NADH-dependent heme degradation system may have a biological role in regulating the concentration of respiratory hemoproteins and the disposition of the aberrant forms of the mitochondrial hemoproteins
-
?
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
involved in heme metabolism
-
?
heme + 2 NADPH + 2 H+ + 2 O2
biliverdin + Fe2+ + CO + 2 NADP+ + H2O
show the reaction diagram
-
involved in heme metabolism
-
?
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 + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
P09601
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
P23711
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q885D4, Q887K9
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q5HSH8
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
O69002, Q88P48, Q9HWR4
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q4K657, Q4K7S1
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
A4Y0Y8
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Q88JR7
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
requires three oxidative reaction steps, via alpha-meso-hydroxy-heme and verdoheme, detailed overview
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
P06762
requires three oxidative reaction steps, via alpha-meso-hydroxy-heme and verdoheme, detailed overview
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
O69002, Q88P48, Q9HWR4
natural electron donor for PigA from Pseudomonas aeruginosa PAO1 is ferredoxin-NADP+-oxidoreductase
-
-
?
heme + 3 AH2 + 3 O2
biliverdin IXalpha + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
-
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin IXalpha + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
H8XZ68
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas fluorescens Pf-5
Q4K657, Q4K7S1
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Rattus norvegicus Sprague-Dawley
P23711
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas syringae DC3000
Q885D4, Q887K9
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas putida KT24400
Q88JR7
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
A4Y0Y8
-
-
-
?
heme + 3 AH2 + 3 O2
biliverdin + Fe2+ + CO + 3 A + 3 H2O
show the reaction diagram
Pseudomonas aeruginosa KT24400
Q88P48
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
-
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
activation of the enzyme leads to induction of the ABC transporter ABCG2, but not of ABCB6
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
biliverdin is involved in hemin degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
CO plays a role in cGMP production, p38 mitogen-activated protein kinase activation, and nuclear factor-kB activation, as part of the heme oxygenase-1/carbon monoxide, HO-1/CO, system, overview, correlation of HO-1-mediated cytoprotection with a decrease in intracellular free iron amounts. Biliverdin is a third generated heme catabolite by HO-1 and is converted to bilirubin by the catalytic reaction of biliverdin reductase. Both compounds are reducing species and hence may play a role in the protective response to vascular injury by oxidative stress
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
endogenous HO-1 shows anti-apoptotic activity, and is overexpressed in various cancer diseases and might contribute to cancer progression
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
exogenous CO activates Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase, resulting in HO-1 expression, mechanism, overview, CO renders endothelial cells resistant to ER stress not only by downregulating C/EBP homologous protein expression via p38 mitogen-activated protein kinase activation but also by upregulating Nrf2-dependent HO-1 expression via PERK activation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P30519
first step in the heme degradation pathway
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heat shock factor 1, HSF1, is directly involved in the transcriptional regulation of ho-1 mediated by the enzyme's cadmium-responsive element, mechanism, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heme degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heme oxygenase is the rate-limiting enzyme in heme degradation to biliverdin, heme oxygenase-1 catalyzes the degradation of heme and forms antioxidant bile pigments as well as the signaling molecule carbon monoxide, HO-1 is inducible in response to a variety of chemical and physical stress conditions to function as a cytoprotective molecule. Catalytic inactive heme oxygenase-1 deletion mutant protein regulates its own expression in oxidative stress in a positive feedback manner, feed-forward autoregulation of HO-1 in oxidative stress, overview, HO-1 protein also plays a role in regulating cadmium chloride-mediated HO-1 gene induction
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
heme oxygenase-1 is regulated by the Nrf2/anti-oxidant response element, ARE, pathway, which plays an important role in regulating cellular anti-oxidants
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
heme oxygenase-1 upregulation significantly inhibits TNF-alpha and Hmgb1 releasing and attenuates lipopolysaccharide-induced acute lung injury in mice, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO is a microsomal enzyme and catalyzes the oxidation of the alpha-meso-carbon bridge of heme moieties resulting in the generation of ferrous iron, carbon monoxide and biliverdin. HO-1 is inducible and plays a main role in the cellular oxidant/antioxidant balance, whereas HO-2 is constitutive and involved in the physiologicalmetabolism of heme
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
HO-1 acts as anti-oxidant and protects cells against injury, it regulates neutrophil O2- production and protects the intestine from damage following EtOH and burn injury, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 catalyzes the rate-limiting step of heme degradation and plays an important anti-inflammatory role via its enzymatic products carbon monoxide and biliverdin
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 exhibits cytoprotective function, enzyme induction, e.g. by dehydrocostus lactone, causes the nuclear accumulation of the nuclear factor E2-related factor 2, Nrf2, and increases the promoter activity of antioxidant response element, ARE, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 gene is a glia-expressing wound-responsive gene, HO-1 gene expression associated with traumatic brain injury involving the toll-like receptor 2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 induction in vivo inhibits cytokine production in synovial tissue, while HO-1 inhibition restores it, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is a cell-protective anti-oxidant enzyme, which is sensitively induced by oxidative stress and regulated by oxidized-1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphocholine, i.e. Ox-PAPC, and Nrf2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is a critical cell defence enzyme against oxidative stress, HO-1 participates in the protective effect afforded by neuronal nicotinic acetylcholine receptors, nAChR, activation, which activates the neuroprotective signaling cascade, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
HO-1 is a heat shock protein, and it provides endogenous anti-oxidant and anti-inflammatory moieties which can modulate colonic inflammation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is a key enzyme in the cellular response to tissue injury and oxidative stress. HO-1 enzymatic activity results in the formation of the cytoprotective metabolites CO and biliverdin
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is an antioxidant and cytoprotective enzyme. Methoxychalcones, especially 5-methoxychalcone, 3,4,5-trimethoxychalcone, and 3,4,5,3',4',5'-hexamethoxychalcone, induce the enzyme expression and activity in macrophages without causing cytotoxicity, they also cause anti-inflamatory affects, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
HO-1 is an inducible enzyme that catalyzes the rate-limiting step in the degradation of heme to biliverdin, CO and iron
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase, CPR, releasing free iron and carbon monoxide
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 is the rate-limiting enzyme in heme degradation
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 participates in the degradation of heme, the enzyme is involved in tumor development
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
HO-1 participates in the degradation of heme, the enzyme is involved in tumor development
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 shows anti-inflammatory effect, inhibition of HO-1 or scavenging of CO significantly reverses the inhibition of LPS-stimulated nitrite accumulation by tanshinone IIA, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
HO-1 shows anti-inflammatory properties
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 shows vasculoprotective and anti-inflammatory activity, it is ptionally regulated by peroxisome proliferator-activated receptors PPARalpha and PPARgamma in vascular cells, inhibition of HO-1 enzymatic activity reverses PPAR ligand-mediated inhibition of cell proliferation and expression of cyclooxygenase-2 in vascular smooth muscle cells, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
HO-1 transcriptional regulation system, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
in aortic smooth muscle cells, induction of HO-1 confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 that is involved in negative regulation of cellular proliferation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
in vascular smooth muscle cells, induction of HO-1 confers vascular protection against cellular proliferation mainly via its up-regulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 that is involved in negative regulation of cellular proliferation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Q5E9F2
induction of HO-1 leads to a reduction of superoxide and increases levels of spermine-NoNoate, HO-1 is involved in artery vascular relaxation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
induction of HO-1 via the ERK-Nrf2-ARE signaling pathway is involved in protecting cells from oxidative stress, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
inhibition or selective knockdown of HO-1 has anti-inflammatory effects via bilirubin, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
statin-induced heme oxygenase-1 increases NF-kappaB activation and oxygen radical production in cultured neuronal cells exposed to lipopolysaccharide, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P09601, P30519
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-1 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
O70252, P14901
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-1 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
O70252, P14901
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-2 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P09601, P30519
the enzyme catalyzes the first and rate-limiting step in the oxidative heme breakdown, physiological role of isozyme HO-2 and its reaction products, detailed overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
the enzyme has anti-inflammatory activity and is involved in mediation of curcumin's inhibitory effect on inducible NO synthase expression and NO production. Treatment with HO inhibitor abolishes the inhibitory effect of curcumin on lipopolysaccharide-induced NF-kappaB activation, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P06762
the enzyme plays a protective role against hypoxic injury, and in the vicious cycle of low-flow priapism
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
P14901
the enzyme shows anti-inflammatory activity, HO-1 expression is induced via the ERK1/2 activation pathway
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
-
the gene encoding HO-1 is a Nrf2-regulated gene. NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells, e.g. by H2O2 and 6-hydroxydopamine
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Mus musculus C57BL/6
P14901
HO-1 shows anti-inflammatory properties
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Mus musculus C57BL/6
-
HO-1 gene is a glia-expressing wound-responsive gene, HO-1 gene expression associated with traumatic brain injury involving the toll-like receptor 2, overview
-
-
?
heme + AH2 + O2
biliverdin + Fe2+ + CO + A + H2O
show the reaction diagram
Mus musculus C3H/HEN
P14901
endogenous HO-1 shows anti-apoptotic activity, and is overexpressed in various cancer diseases and might contribute to cancer progression
-
-
?
additional information
?
-
-
involved in the control of wound healing
-
-
-
additional information
?
-
P06762
butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries involving Nrf2 activation, overview
-
-
-
additional information
?
-
-
capsaicin induces heme oxygenase-1 expression in Hep-G2 cells via activation of PI3K-Nrf2 signaling, and capsaicin protects against SIN-1-induced cytotoxicity, which is abolished by HO-1 inhibition
-
-
-
additional information
?
-
P06762
expression and activity of heme oxygenase-1 is elevated in artificially induced low-flow priapism in rat penile tissues, overview
-
-
-
additional information
?
-
-
expression of Hepatitis C virus core protein sensitizes hepatocytes to toxic injury and inhibits the induction of HO-1 in response to stress, overview
-
-
-
additional information
?
-
-
heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9, overview
-
-
-
additional information
?
-
-
heme oxygenase-1/CO pathway is a key modulator in NO-mediated antiapoptosis and anti-inflammation, mechanisms, overview, mechanisms for the HO-1-mediated inhibition of NO production, activation of the PI3K/Akt pathway, overview
-
-
-
additional information
?
-
-
hemoglobin neurotoxicity is attenuated by inhibitors of the protein kinase CK2 and protein kinase C independent of heme oxygenase activity
-
-
-
additional information
?
-
-
HO-1 and its byproduct biliverdin play major roles in the pathophysiological cascade leading to renal I/R injury
-
-
-
additional information
?
-
P09601
HO-1 gene regulation system, dynamic roles of transcriptional repressor BACH1 and transcription factor NRF2 in the transcription of the heme oxygenase-1 gene, overview
-
-
-
additional information
?
-
-
HO-1 is involved in host defense reactions against various stresses, HO-1 modulates immunocyte activation and functions and suppresses mast cell degranulation, overview
-
-
-
additional information
?
-
-
HO-1 is involved in the function of bax inhibitor-1, BI-1, an anti-apoptotic protein that is located in endoplasmic reticulum membranes and protects cells from endoplasmic reticulum stress-induced apoptosis. For BI-1 associated function, HO-1 expression is induced by nuclear factor erythroid 2-related factor 2, overview
-
-
-
additional information
?
-
-
HO-1 protein delivery mediates activation of various transcription factors, nuclear localization of HO-1 has a signalling role, effect of nuclear localization of HO-1oncell viability, overview
-
-
-
additional information
?
-
-
HO-1 regulation, HO-1 autoregulation, and HO-1 regulatory functions, activation of MAPK pathways is not required in HO-1 self-regulation, overview
-
-
-
additional information
?
-
P14901
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
-
additional information
?
-
P06762
inhibition of heme oxygenase-1 protects against tissue injury in carbon tetrachloride exposed livers, SnPP-IX-mediated HO-1 inhibition markedly aggravates intrahepatic leukocyte-endothelial cell interaction with an almost 2fold increase of the number of adherent leukocytes when compared with solely CCl4-exposed livers, overview
-
-
-
additional information
?
-
P14901
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
-
additional information
?
-
-
NO derived from LPS-induced nitric oxide synthase, NOS, entails an increase in HO activity and this activity, in turn, is involved in the consequent inhibition of NOS, overview
-
-
-
additional information
?
-
P14901
overexpression of HO-1 in B16F10 cells confers resistance to cisplatin treatment, overview
-
-
-
additional information
?
-
-
PMA-dependent activation of HO-1 is mediated via a nonclassical NF-kappaB pathway that is independent of IKK2 activity
-
-
-
additional information
?
-
-
the anti-inflammatory activity of Phellinus linteus is mediated through the PKCdelta/Nrf2/ARE signaling to up-regulation of heme oxygenase-1
-
-
-
additional information
?
-
-
the enzyme activity is positively correlated with nitric oxide and cGMP levels in cavernous tissue, overview
-
-
-
additional information
?
-
-
the enzyme has anti-inflammatory function in the vascular system via production of antioxidants bilirubin and biliverdin as well as CO, the enzyme contributes to cardiovascular health
-
-
-
additional information
?
-
-
the enzyme is involved in cancer cell response to photodynamic therapy, overview
-
-
-
additional information
?
-
-
BphO, a heme oxygenase, produces the linear tetrapyrrole chromophore biliverdin IXa, potential protective role of the BphO reaction product biliverdin, overview
-
-
-
additional information
?
-
-
The first HO reaction step is the regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, the second is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. The third reaction step is a major rate-determining step of HO catalysis to regulate the enzyme activity. HO catalysis is unique in that all three O2 activations are performed by the substrate itself, analysis of structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps, overview. FeOOH verdoheme is the key intermediate of the ring-opening reaction, mechanism, overview. Critical functioning of the FeOOH species in HO heme self-oxidation and catalytic importance of the distal hydrogen bonding network in its unique O2 activation
-
-
-
additional information
?
-
-
The first HO reaction step is the regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, the second is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. The third reaction step is a major rate-determining step of HO catalysis to regulate the enzyme activity. HO catalysis is unique in that all three O2 activations are performed by the substrate itself, analysis of structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps, overview. FeOOH verdoheme is the key intermediate of the ring-opening reaction, mechanism, overview. Critical functioning of the FeOOH species in HO heme self-oxidation and catalytic importance of the distal hydrogenbonding network in its unique O2 activation
-
-
-
additional information
?
-
P06762
The first HO reaction step is the regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, the second is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. The third reaction step is a major rate-determining step of HO catalysis to regulate the enzyme activity. HO catalysis is unique in that all three O2 activations are performed by the substrate itself, analysis of structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps, overview. FeOOH verdoheme is the key intermediate of the ring-opening reaction, mecjanism, overview. Critical functioning of the FeOOH species in HO heme self-oxidation and catalytic importance of the distal hydrogenbonding network in its unique O2 activation
-
-
-
additional information
?
-
O69002, Q88P48, Q9HWR4
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
additional information
?
-
Q88JR7
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
additional information
?
-
Q885D4, Q887K9
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Q4K657, Q4K7S1
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
A4Y0Y8
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Pseudomonas fluorescens Pf-5
Q4K657, Q4K7S1
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Pseudomonas syringae DC3000
Q885D4, Q887K9
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Mus musculus C57BL/6
P14901
LPS-induced maturation of dendritic cells is dependent on STAT3 phosphorylation and independent of HO-1 activity, overview
-
-
-
additional information
?
-
Pseudomonas putida KT24400
Q88JR7
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
additional information
?
-
Mus musculus C3H/HEN
P14901
inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic hepatocellular carcinoma and reduced angiogenesis, mechanism, overview
-
-
-
additional information
?
-
A4Y0Y8
the organism contains two heme oxygenases with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield biliverdin IXalpha, PigA produces the biliverdin isomers IXbeta and IXdelta
-
-
-
additional information
?
-
Pseudomonas aeruginosa KT24400
Q88P48
the organism contains only one enzyme type: PigA. PigA produces the biliverdin isomer IXalpha
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ascorbate
Q5HSH8
-
ferredoxin-NADP+-oxidoreductase
O69002, Q88P48, Q9HWR4
-
ferredoxin-NADP+-oxidoreductase
Q4K657, Q4K7S1
;
ferredoxin-NADP+-oxidoreductase
A4Y0Y8
-
ferredoxin-NADP+-oxidoreductase
Q88JR7
-
ferredoxin-NADP+-oxidoreductase
Q885D4, Q887K9
;
heme
-
hemoprotein, heme is both substrate and cofactor, heme oxygenase-2 binds heme at heme regulatory motifs with a conserved Cys-Pro pair
heme
-
1:1 complex with enzyme
heme
-
heme iron is coordinated by a water molecule in ferric form
heme
-
-
heme
-
high-spin heme oxygenase-2,4-dimethyldeuterohemin-H2O complex dominates at low pH, low-spin heme oxygenase-2,4-dimethyldeuterohemin-OH complex dominates at alkaline pH
heme
P23711
;
NADH
-
NADPH is more effective than NADH
NADPH
-
NADPH is more effective than NADH
NADPH
-
0.5 mM, 16% as effective as NADH
heme
-
the heme is located at the intermonomer interface and is bound by both monomers. The heme iron is coordinated by the side chain of His245 and an azide molecule when it is present in crystallization conditions
additional information
-
CO as a ferrous heme ligand or ferricyanide as an oxidant have no effect
-
additional information
O69002, Q88P48, Q9HWR4
with PigA, there is no difference in product formation whether ferredoxin-NADP+-oxidoreductase or ferredoxin, FNR and ascorbate are used as electron donor
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cd2+
-
0.2 mM, induction of enzyme and 4.5fold enhancement of activity, biliverdin partly prevents
CoCl2
-
activates
Fe2+
-
-
Iron
-
heme oxygenase consists of 3 required protein components: a ferredoxin-like Fe-S cluster protein that can be replaced by ferredoxin, a protein that is inactivated by diethyldicarbonate, inactivation is blocked by heme, a protein with ferredoxin-linked cytochrome c reductase activity
Mg2+
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+-)-1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanol hydrochloride
-
IC50: 0.00006 mM
(+-)-1-(1H-imidazol-1-yl)-4-phenyl-2-butanol hydrochloride
-
IC50: 0.0062 mM
(+-)-4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
IC50: 0.00014 mM
(+-)-4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
IC50: 0.0005 mM
(+-)-4-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
IC50: 0.0014 mM
(+/-)-1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanol hydrochloride
-
-
(+/-)-1-(1H-imidazol-1-yl)-4-phenyl-2-butanol hydrochloride
-
-
(+/-)-4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
-
(+/-)-4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
-
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
P23711
;
(2E)-2-[4-(dimethylamino)benzylidene]hydrazinecarboximidamide
-
binding affinity 0.0229 mM, inhibition of biliverdin production in Escherichia coli expressing the enzyme
(2E)-2-[4-(dimethylamino)benzylidene]hydrazinecarboximidamide
-
binding affinity 0.030 mM
(2E)-2-[[4-(dimethylamino)phenyl]methylidene]hydrazinecarboximidamide
-
binding affinity is 0.0229 mM, complete inhibition
(2E)-2-[[4-(dimethylamino)phenyl]methylidene]hydrazinecarboximidamide
-
binding affinity is 0.030 mM, complete inhibition
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-(methoxymethyl)-1,3-dioxolane hydrochloride monohydrate
-
potent but non-selective inhibitor of HO-2
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-(phenoxymethyl)-1,3-dioxolane hydrochloride
-
potent but non-selective inhibitor of HO-2
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0015 mM
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0008 mM
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane dihydrochloride dihydrate
-
-
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-iodophenoxy)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-methoxyphenoxy)methyl]-1,3-dioxolane hydrochloride
-
moderately high potency and selectivity toward HO-1
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-(hydroxymethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-cyanophenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
potent but non-selective inhibitor of HO-2
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-fluorophenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
potent but non-selective inhibitor of HO-2
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-hydroxyphenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4R)-4-(aminomethyl)-2-[(1H-imidazol-1-yl)methyl]-2-[(2-phenyl)ethyl]-1,3-dioxolane dihydrochloride
-
-
(2R,4R)-4-(azidomethyl)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
moderately high potency and selectivity toward HO-1
(2R,4R)-4-[((4-adamantan-1-yl)phenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4R)-4-[(4-aminophenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane dihydrochloride
-
-
(2R,4R)-4-[(4-bromophenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4R)-4-[(biphenyl-4-yloxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
moderately high potency and selectivity toward HO-1
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)-methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0026 mM
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethyl)pyridin-2-ylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
-
(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-[(4-methoxyphenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
potent but non-selective inhibitor of HO-2
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-nitrophenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(methylthio)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(naphthalen-2-ylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
moderately high potency and selectivity toward HO-1
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
moderately high potency and selectivity toward HO-1
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulphanyl)methyl]-1,3-dioxolane
P09601
-
-
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(pyridin-4-ylsulfanyl)methyl]-1,3-dioxolane dihydrochloride
-
-
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-(fluoromethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
potent but non-selective inhibitor of HO-2
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-chlorophenylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-fluorophenylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(cyclohexylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
moderately high potency and selectivity toward HO-1
(2R,4S)-4-(chloromethyl)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride monohydrate
-
moderately high potency and selectivity toward HO-1
(2R,4S)-4-[(2-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4S)-4-[(3-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
-
(2R,4S)-4-[(4-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
potent but non-selective inhibitor of HO-2
(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
(2S, 4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((4-aminophenyl)thio)methyl]-1,3-dioxolane
P23711
azalanstat, potent inhibitor of HO; azalanstat, potent inhibitor of HO
(2S,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)-methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.02 mM
(2S,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.012 mM
(2Z)-4-[(4-anilinophenyl)amino]-4-oxobut-2-enoic acid
-
binding affinity 0.0156 mM, inhibition of biliverdin production in Escherichia coli expressing the enzyme
(2Z)-4-[(4-anilinophenyl)amino]-4-oxobut-2-enoic acid
-
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
-
binding affinity 0.0122 mM, inhibition of biliverdin production in Escherichia coli expressing the enzyme
(2Z)-N'-[(1Z)-pyridin-3-ylmethylene]-2-(pyridin-3-ylmethylene)hydrazinecarboximidohydrazide
-
binding affinity 0.0159 mM
(2Z)-N'-[(1Z)-pyridin-3-ylmethylidene]-2-(pyridin-3-ylmethylidene)hydrazinecarboximidohydrazide
-
binding affinity is 0.0122 mM, complete inhibition
(2Z)-N'-[(1Z)-pyridin-3-ylmethylidene]-2-(pyridin-3-ylmethylidene)hydrazinecarboximidohydrazide
-
binding affinity is 0.0159 mM, complete inhibition
(R,S)-1-(1H-imidazol-1-yl)-4-phenyl-2-butanol
-
-
(R,S)-1-(4,5-diphenyl-1H-imidazol-1-yl)-4-phenyl-2-butanol
-
-
(R,S)-4-phenyl-1-(1H-1,2,3-triazol-1-yl)-2-butanol
-
-
(R,S)-4-phenyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol
-
-
(R,S)-4-phenyl-1-(1H-tetrazol-1-yl)-2-butanol
-
-
(R,S)-4-phenyl-1-(2H-tetrazol-2-yl)-2-butanol
-
-
(R,S)-4-phenyl-1-(4-phenyl-1H-imidazol-1-yl)-2-butanol
-
-
1-((2-(2-(4-bromophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
; IC50: 0.0019 mM
1-((2-(2-(4-chlorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
; IC50: 0.0043 mM
1-((2-(2-(4-fluorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
; IC50: 0.0038 mM
1-((2-(2-(4-iodophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
; IC50: 0.0037 mM
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-1,2,3-triazole
-
-
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-1,2,4-triazole
-
-
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
; IC50: 0.0007 mM
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-tetrazole
-
-
1-((2-phenylethyl)-1,3-dioxolan-2-yl)methyl-1H-imidazole
-
-
1-((2-phenylethyl-1,3-dioxolan-2-yl)methyl)-4,5-diphenyl-1H-imidazole
-
-
1-((2-phenylethyl-1,3-dioxolan-2-yl)methyl)-4-phenyl-1H-imidazole
-
-
1-(1H-benzimidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(1H-benzotriazol-1-yl)-4-phenyl-2-butanone
-
-
1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone
P09601
-
1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanone hydrochloride
-
; IC50: 0.00011 mM
1-(1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(1H-imidazol-1-yl)-4-phenyl-2-butanone hydrochloride
-
; IC50: 0.004 mM
1-(2,3-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2,4-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2,4-dinitrophenyl)methanamine
-
binding affinity 0.239 mM
1-(2,4-dinitrophenyl)methanamine
-
binding affinity 0.187 mM
1-(2,5-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2,6-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-bromobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-cyanobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-methyl-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(2-methylbenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-methylsulfonyl-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(2-methylthio-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(2-nitro-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(2-nitrobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-phenoxyethyl)-1H-imidazole
-
-
1-(2-phenoxyethyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-phenylethyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2-phenylmethyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(2H-benzotriazol-2-yl)-4-phenyl-2-butanone
-
-
1-(3,4-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3,5-dibromo-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(3,5-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3,5-diphenyl-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(3-bromobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3-cyanobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3-methylbenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3-methylsulfonyl-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(3-methylthio-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(3-nitro-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(3-nitrobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(3-phenyl-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(4,5-dichloro-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(4,5-dicyano-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(4,5-diphenyl-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(4-benzyloxybenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
-
1-(4-bromo-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(4-bromobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-bromophenyl)-2-(1H-imidazol-1-yl)ethanone
-
-
1-(4-bromophenyl)-2-[2-(1-methylethyl)-1H-imidazol-1-yl]ethanone
-
27% inhibition at 0.1 mM
1-(4-bromophenyl)-2-[2-(1-methylethyl)-1H-imidazol-1-yl]ethanone
-
-
1-(4-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-cyanobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-fluorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-iodobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-isopropylbenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-methoxybenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-methylbenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-nitro-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(4-nitrobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-thiomethylbenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(4-trifluoromethylbenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(5-bromo-1H-imidazol-1-yl)-4-phenyl-2-butanone
-
-
1-(5-methylsulfonyl-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(5-methylsulfonyl-1H-tetrazol-1-yl)-4-phenyl-2-butanone
-
-
1-(5-methylsulfonyl-2H-tetrazol-2-yl)-4-phenyl-2-butanone
-
-
1-(5-methylthio-1H-1,2,4-triazol-1-yl)-4-phenyl-2-butanone
-
-
1-(5-methylthio-1H-tetrazol-1-yl)-4-phenyl-2-butanone
-
-
1-(5-methylthio-2H-tetrazol-2-yl)-4-phenyl-2-butanone
-
-
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
P23711
;
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
-
i.e. ADB_901
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
-
-
1-(cyclohexylmethyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-(naphthalen-2-ylmethyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-benzhydryl-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
-
1-bromo-4-phenyl-2-butanone
-
-
1-n-propyl-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
1-[4-(3-bromophenoxy)butyl]-1H-imidazole
-
54% inhibition at 0.1 mM
1-[4-(3-bromophenoxy)butyl]-1H-imidazole
-
-
1-[6-(4-bromophenoxy)exyl]-1H-imidazole
-
-
2-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-2H-1,2,3-triazole
-
-
2-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-2H-tetrazole
-
-
2-(1H-imidazol-1-yl)-1-(4-nitrophenyl)ethanol
-
-
2-(4-chlorophenyl)-N'-[(1E)-1H-indol-3-ylmethylidene]acetohydrazide
-
binding affinity is 0.0141 mM, complete inhibition
2-(4-chlorophenyl)-N'-[(1E)-1H-indol-3-ylmethylidene]acetohydrazide
-
binding affinity is 0.0158 mM, complete inhibition
2-(4-chlorophenyl)-N'-[(1Z)-1H-inden-3-ylmethylene]acetohydrazide
-
binding affinity 0.0141 mM, inhibition of biliverdin production in Escherichia coli expressing the enzyme
2-(4-chlorophenyl)-N'-[(1Z)-1H-inden-3-ylmethylene]acetohydrazide
-
binding affinity 0.0158 mM, above 0.25 mM significant decrease in growth of strain on heme as sole source of iron
2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole
P23711
-
2-mercaptoethanol
-
0.1 mM, 81% inhibition
2-methylthio-1H-imidazole
-
-
2-oxy-substituted 1-(1H-imidazol-1-yl)-4-phenylbutanes
-
-
2-[2-(4-bromophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
-
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
-
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
1 mM, potent inhibitor
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
IC50: 0.004 mM
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dithiolane
-
IC50: 0.0047 mM
2-[2-(4-fluorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
-
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
-
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl)methyl]1,3-dioxolane
P09601
-
3,5-dibromo-1H-1,2,4-triazole
-
-
3,5-diphenyl-1H-1,2,4-triazole
-
-
3-morpholinosydnonimine
-
NO-donor, 27% inhibition of recombinant heme oxygenase-2
3-phenyl-1H-1,2,4-triazole
-
-
4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
; IC50: 0.0017 mM
4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
; IC50: 0.0047 mM
4-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
; IC50: 0.0027 mM
4-hydroxymercuribenzoate
-
1 mM, complete inhibition
4-oxo-4-[[4-(phenylamino)phenyl]amino]butanoic acid
-
binding affinity is 0.0156 mM, complete inhibition
4-oxo-4-[[4-(phenylamino)phenyl]amino]butanoic acid
-
binding affinity is 0.0201 mM, complete inhibition
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
-
-
4-phenyl-1-(1H-1,2,3-triazol-1-yl)-2-butanone
-
-
4-phenyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone
-
the inhibitor binds at the distal pocket through the coordination of heme iron by the N4 in the triazole mpiety, whereas the phenyl group is stabilized by hydrophobic interactions from residues within the binding pocket, binding structure, modelling, overview
4-phenyl-1-(1H-1,2,4-triazol-1-yl)butan-2-one
-
-
4-phenyl-1-(1H-imidazol-1-yl)-2-butanone
P09601
-
-
4-phenyl-1-(1H-pyrazol-1-yl)-2-butanone
-
-
4-phenyl-1-(1H-tetrazol-1-yl)-2-butanone
-
-
4-phenyl-1-(2-phenyl-1H-imidazol-1-yl)-2-butanone
-
-
4-phenyl-1-(2H-1,2,3-triazol-2-yl)-2-butanone
-
-
4-phenyl-1-(2H-tetrazol-2-yl)-2-butanone
-
-
4-phenyl-1-(4-phenyl-1H-imidazol-1-yl)-2-butanone
-
-
4-phenyl-1-(5-phenyl-1H-tetrazol-1-yl)-2-butanone
-
-
4-phenyl-1-(5-phenyl-2H-tetrazol-2-yl)-2-butanone
-
-
4-[(2-hydroxyphenyl)amino]naphthalene-1,2-dione
-
binding affinity is 0.0288 mM, partial inhibition
4-[(2-hydroxyphenyl)amino]naphthalene-1,2-dione
-
binding affinity is 0.0728 mM, partial inhibition
azalanstat
-
; IC50: 0.0053 mM
azalanstat
-
IC50: 0.006 mM
azalanstat
-
-
azalanstat
P09601
;
azide
-
binding structure, NMR analysis, overview
benzyl isocyanide
-
most potent uncompetitive inhibitor with respect to heme, is the strongest ligand to ferrous heme
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
calmidazolium chloride
-
inhibition of calmodulin-stimulation, 50% inhibition at 0.008 mM
chromium protoporphyrin
P09601
;
-
CO
-
the third reaction step is inhibited by CO
Co-protoporphyrin
-
0.005 mM, 82.5% inhibition of kidney heme oxygenase
Co-protoporphyrin
-
-
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
cobalt protoporphyrin
-
i.e. CoPP, significantly reduces the viability of glioma cells C6 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
Cr-containing protoporphyrin IX
-
potent inhibitor
-
cyanide
-
binding structure, NMR analysis, overview
cysteine
-
1 mM, 67% inhibition
dimethyl 1-(2-oxo-4-phenylbut-1-yl)-1H-imidazole-4,5-dicarboxylate
-
-
dithiothreitol
-
0.01 mM, 88% inhibition
DTE
-
binding structure, overview
DTE
-
shows high-affinity binding, structure, overview
DTE
P06762
shows high-affinity binding, structure, overview
DTT
-
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
DTT
P06762
shows high-affinity binding, structure, overview. The noncoordinating thiol group of DTT is critical for its high affinity to the mammalian HO
ethyl (1-(2-oxo-4-phenylbutyl)-1H-tetrazol-5-yl)acetate
-
-
ethyl (2-(2-oxo-4-phenylbutyl)-2H-tetrazol-5-yl)acetate
-
-
ethyl 1-(2-oxo-4-phenylbut-1-yl)-1H-imidazole-2-carboxylate
-
-
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
Ferric protoporphyrin
-
i.e. FePP or hemin, significantly reduces the viability of glioma cells C6 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
FR180204
-
ERK inhibitor, reduces baseline culture HO activity, without altering the activity of recombinant HO-1 or HO-2
Hg2+
-
0.3 mM, complete inhibition
Hg2+
-
inhibition of NADPH-cytochrome c reductase or biliverdin reductase in reconstituted heme oxygenase system
iodoacetamide
-
5 mM, 39% inhibition, 10 mM, 79% inhibition
isopropyl isocyanide
-
-
isopropyl isocyanide
-
binding affinity is the weakest for HO-1. HO-2 displays a similar trend
ketoconazole
P23711
;
methyl 1-(2-oxo-4-phenylbut-1-yl)-1H-1,2,4-triazole-3-carboxylate
-
-
methyl 1-(2-oxo-4-phenylbut-1-yl)-1H-1,2,4-triazole-5-carboxylate
-
-
methyl 1-(2-oxo-4-phenylbut-1-yl)-1H-imidazole-4-carboxylate
-
-
methyl 1-(2-oxo-4-phenylbut-1-yl)-1H-imidazole-5-carboxylate
-
-
N'-(pyridin-4-ylcarbonyl)pyridine-4-carbohydrazide
-
binding affinity is 0.0335 mM, partial inhibition
N'-(pyridin-4-ylcarbonyl)pyridine-4-carbohydrazide
-
binding affinity is 0.0447 mM, partial inhibition
N-(4-imidazo[1,2-a]pyridin-2-ylphenyl)-2-nitrobenzamide
-
binding affinity is 0.0209 mM, complete inhibition
N-(4-imidazo[1,2-a]pyridin-2-ylphenyl)-2-nitrobenzamide
-
binding affinity is 0.0061 mM, complete inhibition
N-(4-imidazo[1,2-a]pyridin-2-ylphenyl)-3-nitrobenzamide
-
binding affinity 0.0209 mM, inhibition of biliverdin production in Escherichia coli expressing the enzyme
N-(4-imidazo[1,2-a]pyridin-2-ylphenyl)-3-nitrobenzamide
-
binding affinity 0.0061 mM
n-butyl isocyanide
-
-
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
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
inhibition of NADPH-cytochrome c reductase in reconstituted heme oxygenase system
pegylated zinc protoporphyrin
P09601
inhibition of isozyme HO-1
-
Porphyrins
-
metalloporphyrins, decreasing order of inhibition potency: Sn-mesoporphyrin, Sn-protoporphyrin, Zn-protoporphyrin, Mn-protoporphyrin, Co-protoporphyrin
Porphyrins
-
beta, gamma and delta-oxyprotohaem IX
Porphyrins
-
protoporphyrin IX, Zn-protoporphyrin IX, 2,4-diacetyldeuteroporphyrin IX, deuteroporphyrin IX, coproporphyrin II, III and IV
Porphyrins
-
Ni, Mn, and Sn-protoporphyrin IX; overview
Porphyrins
-
Zn-deuteroporphyrin IX 2,4-bis glycol, synthetic metal porphyrins
Porphyrins
-
metalloporphyrins
S-nitroso-N-acetyl-pennicillamine
-
NO-donor, 23% inhibition of recombinant heme oxygenase-2
SL327
-
MEK inhibitor, reduces baseline culture HO activity, without altering the activity of recombinant HO-1 or HO-2
Sn protoporphyrin IX
-
-
Sn(IV) protoporphyrin IX dichloride
-
SnPP
Sn-protoporphyrin
-
0.005 mM, complete inhibition of kidney heme oxygenase
Sn-protoporphyrin
-
-
Sn-protoporphyrin
-
0.002 mM, 80% inhibition
Sn-protoporphyrin
-
-
Sn-protoporphyrin
-
0.001 mM, 84% inhibition of HO-1, 99% inhibition of HO-2
Sn-protoporphyrin
P06762
SnPP-IX-mediated HO-1 inhibition markedly aggravates intrahepatic leukocyte-endothelial cell interaction with an almost 2fold increase of the number of adherent leukocytes when compared with solely CCl4-exposed livers
Sn-protoporphyrin
-
-
Sn-protoporphyrin IX
-
i.e. SNPPIX
Sn-protoporphyrin IX
-
Sn-PPIX, inhibits the enzyme and reduces the activating effect of lipopolysaccharides
sodium nitroprusside
-
NO-donor, 58% inhibition of recombinant heme oxygenase-2
thioglycerol
-
binds weakly, shows high affinity to the mammalian HO
thioglycerol
-
binds with 10fold lower affinity than DTT, shows high affinity to the mammalian HO
thioglycerol
P06762
binds with 10fold lower affinity than DTT, shows high affinity to the mammalian HO
tin mesoporphyrin
-
-
tin protoporphyrin
-
SnPP, specific HO-1 inhibition abrogating the inhibition of COX-2 expression by Wy-14,643
tin protoporphyrin
-
SnPP
tin protoporphyrin
-
i.e. SnPP, does not affect the viability of glioma cells GBM8401 in the absence of serum
tin protoporphyrin
-
i.e. SnPP, does not affect the viability of glioma cells C6 in the absence of serum
tin protoporphyrin
-
-
tin protoporphyrin
P09601
;
tin protoporphyrin IX
-
-
tinmesoporphyrin
-
competitive specific inhibitor
U0126
-
MEK inhibitor, reduces baseline culture HO activity, without altering the activity of recombinant HO-1 or HO-2
zinc protoporphyrin
-
dose-dependently increases SMC proliferation, induced by either platelet-derived growth factor or 15% fetal bovine serum
zinc protoporphyrin
P06762
ZnPP, supresses enzyme induction and inhibits HO-1, it also abolishes the anti-colitic effect of 5-aminosalicylic acid
zinc protoporphyrin
-
ZnPP
zinc protoporphyrin
-
-
zinc protoporphyrin
-
-
zinc protoporphyrin
P09601
; low inhibition
zinc protoporphyrin IX
-
0.005 mg/kg, 82% inhibition
-
zinc protoporphyrin IX
-
ZnPP, high-loading nanosized micelles of copoly(styrene-maleic acid)-zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor, method development, overview
-
zinc protoporphyrin IX
-
Zn(II)PPIX, a selective HO-1 inhibitor, Zn(II)PPIX exerts dose-dependent antitumor effects and shows retardation of tumor growth
-
zinc protoporphyrin IX
P14901
Zn(II)PPIX, a selective HO-1 inhibitor, Zn(II)PPIX exerts dose-dependent antitumor effects and shows retardation of tumor growth
-
zinc protoporphyrin IX
-
activity of both recombinant isoenzymes HO-1 and HO-2 is strongly inhibited
-
zinc(II) deuteroporphyrin IX-2, 4-bisethyleneglycol
-
-
zinc-protoporphyrin
P14901
ZnPPIX
Zn (II) protoporphyrin IX
-
a specific HO-1 inhibitor, inhibition of HO-1 activity by Zn (II) protoporphyrin IX, a specific HO-1 inhibitor, prevents the suppression of TNF-alpha production. The cytokine inhibition by HO-1 is associated with selective suppression of the DNA-binding activity of AP-1 transcription factors
Zn protoporphyrin
-
-
Zn protoporphyrin IX
-
pretreatment prior to administration of Cd2+, decrease of enzyme activity to half
Zn(II) protoporphyrin IX
-
0.02 mM, potent inhibitor
Zn(II) protoporphyrin IX
-
i.e. ZnPP
Zn(II) protoporphyrin IX
-
mitigates brazilin-induced activity of HO-1 and inhibition of NO, PEG2, TNF-alpha and IL-1beta production in lipopolysaccharide-stimulated RAW264.7 macrophages
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
Zn-protoporphyrin
-
-
Zn-protoporphyrin
-
0.001 mM, 87% inhibition of HO-1, 91% inhibition of HO-2
Mn-protoporphyrin
-
-
additional information
-
synthesis of a series of 2-oxy-substituted 1-(1H-imidazol-1-yl)-4-phenylbutanes comprising imidazole-ketones, imidazole-dioxolanes, and imidazole-alcohols substituted with halogens in the phenyl ring, evaluation of the inhibitory potency on heme oxygenase, overview
-
additional information
P09601
imidazole-based inhibitor derivatives, overview; imidazole-based inhibitor derivatives, overview
-
additional information
O70252, P14901
imidazole-based inhibitor derivatives, overview; imidazole-based inhibitor derivatives, overview
-
additional information
-
no inhibition by phosphatidylinositol 3-kinase inhibitors LY294002 and LY303511, by 4,5,6,7-tetrabromobenzotriazole, 2-dimethyl-amino-4,5,6,7-tetrabromo-1H-benzimidazole, and by the PKC inhibitor GF109203X
-
additional information
P06762
EtOH combined with burn injury significantly increases neutrophil O2- production and p47phox and p67phox activation and decreases caspase-3 activity and apoptosis, accompanied with a decrease in neutrophil HO-1 levels, overview
-
additional information
-
dexamethasone does not modify HO-2 activity
-
additional information
-
whereas equilibrium binding of the isocyanides to ferric human heme oxygenases is rapid, binding to ferric Hmx1 is much slower
-
additional information
-
HO-1-generated hydrogen peroxide leads to a decrease in HO-1 activity
-
additional information
-
azole-based, HO-1 inhibitors act in a non-competitive manner with respect to heme. These inhibitors bind to the distal side of heme in the heme-binding pocket with the imidazolyl group in the eastern region of the inhibitor serving as an anchor by coordinating with the heme iron. The western region of the respective inhibitors fits into a hydrophobic pocket that extends back towards the distal side of the heme-binding pocket. The inherent flexibility of the distal helix results in the opening up of the heme-binding pocket so as to accommodate the inhibitor
-
additional information
P23711
azole-based, HO-1 inhibitors act in a non-competitive manner with respect to heme. These inhibitors bind to the distal side of heme in the heme-binding pocket with the imidazolyl group in the eastern region of the inhibitor serving as an anchor by coordinating with the heme iron. The western region of the respective inhibitors fits into a hydrophobic pocket that extends back towards the distal side of the heme-binding pocket. The inherent flexibility of the distal helix results in the opening up of the heme-binding pocket so as to accommodate the inhibitor
-
additional information
-
design and synthesis, and inhibitory potency of a series of 2-oxy-substituted 1-azolyl-4-phenylbutanes, inhibition of heme oxygenase-1 and heme oxygenase-2, overview
-
additional information
-
development of HO-specific inhibitors targeting the critical distal hydrogen bonding network, e.g. thiol compounds, overview. HmuO exhibits similar affinity for DTT, DTE, and thioglycerol in contrast to the mammalian enzyme, indicating no functionality of the noncoordinating thiol group in complex formation with this bacterial HO
-
additional information
-
development of HO-specific inhibitors targeting the critical distal hydrogen bonding network, e.g. thiol compounds, overview. Thiol binding significantly suppresses but does not completely interrupt the reduction of the ferric heme to the ferrous state. HO is inhibited thus at higher thiol concentration than expected from the dissociation equilibrium constants
-
additional information
P06762
development of HO-specific inhibitors targeting the critical distal hydrogen bonding network, e.g. thiol compounds, overview. Thiol binding significantly suppresses but does not completely interrupt the reduction of the ferric heme to the ferrous state. HO is inhibited thus at higher thiol concentration than expected from the dissociation equilibrium constants
-
additional information
P23711
selective inhibition of heme oxygenase-2 activity by analogues of 1-(4-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole (clemizole), exploration of the effects of substituents at the N-1 position, overview. Many of the compounds are potent and highly selective for the constitutive HO-2 isozyme, but show substantially less inhibitory activity against the inducible HO-1 isozyme
-
additional information
-
synthesis and inhibitory potency on isozyme HO-1 of imidazole-based compounds, molecular docking and modelling, overview. No inhibition by 1-[6-(4-bromophenoxy)exyl]-1H-imidazole, 1-(2-phenoxyethyl)-1H-imidazole, 2-(1H-imidazol-1-yl)-1-(4-nitrophenyl)ethanol, and 1-(4-bromophenyl)-2-(1H-imidazol-1-yl)ethanone
-
additional information
-
synthesis and inhibitory potency on isozyme HO-1 of imidazole-based compounds, molecular docking and modelling, overview
-
additional information
P09601
metalloporphyrins are used as competitive enzyme inhibitors. Development of isozyme-selective heme oxygenase inhibitors. Development and evaluation of non-competitive inhibitors with selectivity for isozyme HO-1, and synthesis and analysis of a series of 2-oxy-substituted 1-(1H-imidazol-1-yl)-4-phenylbutanes, overview. Synthesis of a series of alpha-(1H-imidazol-1-yl)-omega-phenylalkanes to examine the effect of introducing heteroatoms into the central alkyl linker. Imidazole-dioxolane-based HO inhibitors are all selective for HO-1, and exhibit substantially lower activity towards HO-2. HO-1-inhibitor, binding mechanism, detailed overview. HO-1 inducible binding mode, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,4,6-Trinitrobenzene sulfonic acid
P06762
induces HO-1 expression in the colon and stimulates its catalytic activity
5-aminosalicylic acid
P06762
induces HO-1 expression in the colon and stimulates its catalytic activity
ascorbate
-
addition of a second electron donor like ascorbate leads to 10times faster heme conversion
brazilin
-
main constituent of Caesalpinia sappan, induces HO-1 expression in a concentration-dependent manner at 0.01-0.3 mM at the level of protein synthesis, thus without affecting mRNA transcription of HO-1
Calmodulin
-
calcium-dependent binding to enzyme, 3fold increase in catalytic activity
Co protoporphyrin IX
-
activates and induces HO-1
Co-protoporphyrin
-
-
cobalt protoporphyrin IX
-
1 mg/kg, 5.9fold increase of activity
cobalt protoporphyrin IX chloride
P06762
Copp, a HO-1 activator
cysteine
-
0.1 mM, slight stimulation, inhibition at 1 mM
Fe/S cluster
-
heme oxygenase consists of 3 required protein components: a ferredoxin-like Fe-S cluster protein that can be replaced by ferredoxin, a protein that is inactivated by diethyldicarbonate, inactivation is blocked by heme, a protein with ferredoxin-linked cytochrome c reductase activity
heme
-
-
Propionate
-
the enzyme requires only a single propionate interacting with the buried terminus of Lys16 to exhibit full activity, and it tolerates the existence of a propionate at the exposed 8-position
sildenafil
-
-
SnCl2
-
is a potent and specific inducer of renal HO-1 expression and activity
tadalafil
-
-
vardenafil
-
-
lipopolysaccharide
-
activates the enzyme, activation is partly reduced by addition of inhibitor Sn-protoporphyrin
additional information
-
gamma-irradition of 0.5 Gy/min dose power causes a significant increase of activity
-
additional information
Q94FX1
enzyme activity is increased by 7.5 and 15 kJ/squaremeter UV-B doses
-
additional information
-
hemin and taurine chloramine, Tau-Cl, raise the transcription of the gene encoding HO-1
-
additional information
-
capsaicin, i.e. trans-8-methyl-N-vanillyl-6-nonenamide, induces heme oxygenase-1 expression in Hep-G2 cells via activation of PI3K-Nrf2 signaling
-
additional information
-
far infrared irradiation induces HO-1 protein, mRNA and promoter activity through heat stress which activates the antioxidant responsive element/NF-E2-related factor-2 complex, overview
-
additional information
-
tranilast, i.e. N-[3',4'-dimethoxycinnamonyl] anthranilic acid, an orally active anti-allergic drug, tranilast induces heme oxygenase-1 expression through the extracellular signal-regulated kinase-1/2 pathway in RAW264.7 macrophages. Effects of tranilast on LPS-induced PGE2, NO, TNF-alpha, and IL-1beta production are partially reversed by the HO-1 inhibitor tin protoporphyrin, overview. UO126 significantly inhibits tranilast-induced HO-1 expression, but neither SB203580 nor SP600125 have a significant effect on HO-1 expression by tranilast
-
additional information
-
epigallocatechin activates heme oxygenase-1 expression via protein kinase Cdelta, not PKCalpha and PKCbeta, and Nrf2, siRNA knock down of Nrf2 significantly inhibits EGC-induced HO-1 expression, inhibition of PKCdelta, e.g. by Ro-31-8220, decreases EGC-induced HO-1 mRNA expression, whereas MAP kinase and phosphatidylinositol-3-kinase pathway inhibitors have no significant effect, overview
-
additional information
-
at low concentrations curcumin induces the expression of HO-1 in RAW264.7 macrophages
-
additional information
P06762
butylated hydroxyanisole stimulates heme oxygenase-1 gene expression after rat carotid artery injury, overview
-
additional information
-
HO-1 expression, prooxidative activity, and cytotoxicity are increased after treatment with heme, heavy metals, and peroxides compared to control cells
-
additional information
-
heme oxygenase-1 is induced by tert-butylhydroquinone and by deltamethrin via activation of Nrf2, overview
-
additional information
-
methoxychalcones, especially 5-methoxychalcone, 3,4,5-trimethoxychalcone, and 3,4,5,3',4',5'-hexamethoxychalcone, induce the enzyme expression and activity in macrophages, overview, increase in heme oxygenase activity and HO-1 protein expression mediated by CH25 is significantly attenuated by the presence of an inhibitor of PI3K LY2940002, as well as by the addition of the glutathione precursor NAC
-
additional information
-
exogenous CO activates Nrf2 through the phosphorylation of protein kinase R-like endoplasmic reticulum kinase, PERK, resulting in HO-1 expression
-
additional information
-
dehydrocostus lactone induces HO-1 expression in Hep-G2 cells, while mokko lactone, a reduced product of dehydrocostus lactone, and alpha-methyl-gamma-butyrolactone, a parent structure of mokko lactone, do not induce HO-1 expression
-
additional information
P06762
HO-1 is a heat shock protein with anti-inflammatory activity
-
additional information
-
curcumin, but not its metabolite tetrahydrocurcumin, induces HO-1 expression and growth inhibition of aortic smooth muscle cells through Nrf2-dependent antioxidant response element, ARE, activation, mechanism, overview, curcumin is isolated from the rhizomes of turmeric
-
additional information
-
curcumin, but not its metabolite tetrahydrocurcumin, induces HO-1 expression and growth inhibition of vascular smooth muscle cells through Nrf2-dependent antioxidant response element, ARE, activation, mechanism, overview, curcumin is isolated from the rhizomes of turmeric
-
additional information
-
triphlorethol-A, i.e. 2-[2-(3,5-dihydroxyphenoxy)-3,5-dihydroxyphenoxy]benzene-1,3,5-triol, a phlorotannin isolated from Ecklonia cava, induces heme oxygenase-1 via activation of ERK and NF-E2 related factor 2 transcription factor, triphlorethol-A increases nuclear translocation, ARE, binding, and transcriptional activity of Nrf2, transcription factor Nrf2 regulates antioxidant response element, ARE, of phase 2 detoxifying and antioxidant enzymes, requirement for ERK activation in the induction of HO-1 expression by triphlorethol-A because an ERK inhibitor significantly reduces HO-1 protein expression in response to triphlorethol-A, overview
-
additional information
-
HO-1 is inducible in response to a variety of chemical and physical stress conditions to function as a cytoprotective molecule, hemin and cadmium chloride-mediated HO-1 induction, overview
-
additional information
-
hemin induces heme oxygenase-1 expression in human umbilical vein endothelial cells
-
additional information
P14901
cobalt protoporphyrin, CoPPIX, induces HO-1
-
additional information
-
the enzyme is induced by 5-aminolevulinic acid, the activation is reduced to 29% by gene silencing with siRNA, overview
-
additional information
-
HO-1 is strongly induced in the skin after long wave ultraviolet radiation, UVA-1 irradiation generates oxidized phospholipids derived from 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine that mediate the expression of HO-1 in skin cells, epoxyisoprostanephosphatidylcholine also induces the enzyme in the skin, overview
-
additional information
-
the PKCdelta/Nrf2/ARE signaling up-regulates heme oxygenase-1
-
additional information
-
induction of HO-1 by hemin and Zn2+-protoporphyrin IX in presence or absence of light, Nrf2-dependent induction of human ABC transporter ABCG2 and heme oxygenase-1 in HepG2 cells by photoactivation of porphyrins, overview
-
additional information
-
cobalt protoporphyrin, CoPPIX, induces the enzyme, molecular mechanism, overview, CoPPIX inhibits STAT3 phosphorylation and the LPS-mediated maturation of bone marrow-derived dendritic cells independently of HO-1
-
additional information
-
the HO-1 gene is transcriptionally induced by the phorbol ester PMA in cell cultures of monocytic cells with a regulatory pattern that is different from that of LPS-dependent HO-1 induction in these cells, overview, the upregulation is abrogated in embryonic fibroblasts from p65-/- mice, antioxidant N-acetylcysteine and inhibitors of p38 MAPK or serine/threonine kinase CK2 also block the upregulating effect of PMA, thus induction of HO-1 gene expression by PMA is regulated via an IkappaB kinase-independent, atypical NFkappaB pathway that is mediated via the activation of p38 MAPK and CK2, overview, PMA-dependent HO-1 gene activation requires IkappaBalpha, but notIKK2
-
additional information
-
the HO-1 gene is transcriptionally induced by the phorbol ester PMA, mediated via a newly identified kappaB element of the proximal rat HO-1 gene promoter region, overview
-
additional information
-
oxidized-1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphocholine, i.e. Ox-PAPC, induces HO-1 involving Nrf2 activation, the transcriptional activation is regulated by the plasma membrane electron transport complex, PMET, containing ecto-NADH oxidase 1, eNOX1, and NADPH:quinone oxidoreductase 1, NQO1. Chemical inhibitors of PMET system and siRNAs to PMET components NQO1 and eNOX1, as well as exogenous NAD(P)H significantly decrease HO-1 induction by Ox-PAPC
-
additional information
-
HO-1 is induced by epibatidine via neuronal nicotinic acetylcholine receptors and ERK1/2 in the neuroprotective signaling cascade, overview
-
additional information
P14901
striatal blood injection increases HO activity, and oxidative stress induces the enzyme, overview
-
additional information
-
the enzyme expression is induced by enterolactone from enterobacteria through activation of nuclear factor-E2-related factor 2, Nrf2, in endothelial cells
-
additional information
-
the enzyme activity is positively correlated with nitric oxide and cGMP levels in cavernous tissue, overview
-
additional information
P06762
CCl4 induces HO-1 expression in the liver
-
additional information
-
HO-1 is induced by NO in macrophages and hepatocytes inhibiting apoptotic cell death of hepatocytes via the regulation of cellular homeostasis of prooxidant iron
-
additional information
-
tanshinone IIA from Salvia miltiorrhiza induces heme oxygenase-1 expression via intracellular production of reactive oxygen species, and inhibits lipopolysaccharide-induced nitric oxide expression in RAW 264.7 cells. Inhibition of HO-1 or scavenging of CO significantly reverses the inhibition of LPS-stimulated nitrite accumulation by tanshinone IIA, signaling pathways, overview. Activation of PI 3-K and ERK signaling pathways are required for tanshinone-induction of HO-1 protein expression in RAW 264.7 macrophages
-
additional information
-
ferric protoporphyrin IX enhances the HO-1 expression in MCF-7 cells
-
additional information
-
vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-beta and reactive oxygen species generation in human retinal pigment epithelial cells. Activator protein-1 binding sites are located in the promoter region of HO-1, and TGF-beta also induces the enzyme, while inhibitors of TGF-beta signaling, e.g. SB431542 or TGF-beta-neutralizing antibodies, decrease the vitreous induction of HO-1, but PD98059, an inhibitor of the ERK pathway, has no effect on HO-1 induction, overview
-
additional information
-
the toll-like receptor 2 is involved in HO-1 induction in glial cells, 34fold induction of HO-1 by stab-wound injury in wild-type mice, overview
-
additional information
-
dexamethasone does not modify HO-2 activity; hemin is an inducer of HO-1, additive effect of hemin with dexamethasone, overview
-
additional information
P09601
oxidative stress and arsenite strongly induce HMOX1, heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1, BACH1 repression is dominant over NRF2-mediated HMOX1 transcription and inactivation of BACH1 is a prerequisite for HMOX1 induction, but nuclear accumulation of NRF2 is not necessary for HMOX1 induction
-
additional information
P14901
lipopolysaccharide, from Escherichia coli, serotype 0127:B8, upregulates the expression of HO-1 in adult and fetal mouse liver, maternal LPS exposure results in oxidative stress in fetuses, which may contribute to LPS-induced developmental toxicity, LPS-induced upregulation of HO-1 is blocked by alpha-phenyl-N-t-butylnitrone, PBN, a free radical spin trapping agent, overview
-
additional information
-
simvastatin induces the enzyme in neurons, HO-1 upregulation is significantly associated with increased nuclear factor kappa B activation, manifested as IkappaBalpha phosphorylation and p65 nuclear translocation, as well as increased production of superoxides, inhibition of the effects by zinc protoporphyrin
-
additional information
-
dependence of bphOP expression on RpoS
-
additional information
-
positive correlation between seminal plasma HO enzyme activity and sperm concentration, sperm motility percentage, motile spermatozoa ml-1 and sperm normal morphology per cent
-
additional information
-
heme turnover is promoted by light when spinach thylakoids are present
-
additional information
-
a higher dilauroylphosphatidylcholine/HO-1 ratio than typically used provides an improved environment for HO-1 activity
-
additional information
-
no significant changes in HO-1 mRNA levels between ethanol treated and pair-fed control
-
additional information
-
the proximal residue histidine 25 plays a key role in HO-1 activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0036
alpha-meso-oxyprotoheme IX
-
-
-
0.125
Co-heme
-
-
0.017
Fe-heme
-
-
0.01
hematoheme
-
-
0.00024
heme
-
heme oxygenase-1
0.00067
heme
-
heme oxygenase-2
0.00093
heme
-
-
0.00236
heme
D9IWR7
pH 7.2, 37C, recombinant enzyme
0.0027
heme
-
HO3, without ascorbate
0.003
heme
-
recombinant C-terminal truncated heme oxygenase-1
0.003
heme
-
heme oxygenase-1, wild-type
0.0038
heme
-
in the absence of bovine serum albumin
0.005
heme
-
in the presence of bovine serum albumin
0.005
heme
-
HO-1
0.0057
heme
-
HO4, without ascorbate
0.006
heme
-
recombinant heme oxygenase-1/cytochrome P450 reductase fusion protein
0.014
heme
-
heme oxygenase-1, H132G and H132A mutants
0.018
heme
-
heme oxygenase-1, H132S mutant
0.0242
heme
Q4K657, Q4K7S1
PigA, pH and temperature not specified in the publication
0.0269
heme
O69002, Q88P48, Q9HWR4
pH and temperature not specified in the publication
0.0269
heme
Q88JR7
pH and temperature not specified in the publication
0.04
heme
-
-
0.0009
heme b
-
spleen heme oxygenase
0.029
heme c
-
spleen heme oxygenase
0.0061
NADPH
-
-
0.023
NADPH
-
-
0.0009
protoheme
-
-
0.0018
protoheme IX
-
-
0.005
protoheme IX
-
enzyme from spleen and liver
0.0164
protoheme IX
-
enzyme from spleen
0.01
Hemin
-
intestinal enzyme
additional information
additional information
H8XZ68
Michaelis-Menten kinetics, overview
-
additional information
additional information
O69002, Q88P48, Q9HWR4
Michaelis-Menten kinetics for PigA, overview
-
additional information
additional information
Q4K657, Q4K7S1
Michaelis-Menten kinetics for PigA, overview
-
additional information
additional information
Q88JR7
Michaelis-Menten kinetics for PigA, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0583
heme
-
-
0.32
heme
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0015
benzyl isocyanide
-
HO-1
0.000082
Co-protoporphyrin
-
-
0.00012
copoly(styrene-maleic acid)-zinc protoporphyrin
-
-
0.000033
Sn-protoporphyrin
-
-
0.00013
Zn-protoporphyrin
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00006
(+-)-1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanol hydrochloride
-
IC50: 0.00006 mM
0.0062
(+-)-1-(1H-imidazol-1-yl)-4-phenyl-2-butanol hydrochloride
-
IC50: 0.0062 mM
0.00014
(+-)-4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
IC50: 0.00014 mM
0.0005
(+-)-4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
IC50: 0.0005 mM
0.0014
(+-)-4-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
IC50: 0.0014 mM
0.06
(+/-)-1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanol hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
1.8
(+/-)-1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanol hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
6.2
(+/-)-1-(1H-imidazol-1-yl)-4-phenyl-2-butanol hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
16
(+/-)-1-(1H-imidazol-1-yl)-4-phenyl-2-butanol hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.14
(+/-)-4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
2.6
(+/-)-4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.5
(+/-)-4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
4
(+/-)-4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.00006
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
P23711
substitution of the chlorophenyl group in the western region to a iodophenyl group
0.00014
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
P23711
substitution of the chlorophenyl group in the western region to a bromophenyl group
0.0014
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
P23711
substitution of the chlorophenyl group in the western region to a fluorophenyl group
0.004
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
P23711
-
0.0062
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
P23711
substitution of the chlorophenyl group in the western region to a phenyl group
0.00173
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-(methoxymethyl)-1,3-dioxolane hydrochloride monohydrate
-
HO-1
0.0033
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-(methoxymethyl)-1,3-dioxolane hydrochloride monohydrate
-
HO-2
0.00059
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-(phenoxymethyl)-1,3-dioxolane hydrochloride
-
HO-1
0.0016
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-(phenoxymethyl)-1,3-dioxolane hydrochloride
-
HO-2
0.0008
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0008 mM
0.0015
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0015 mM
0.01
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane dihydrochloride dihydrate
-
HO-1
0.026
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane dihydrochloride dihydrate
-
HO-2
0.009
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-iodophenoxy)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.015
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-iodophenoxy)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.00133
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-methoxyphenoxy)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.019
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-methoxyphenoxy)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.012
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-(hydroxymethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.1
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-(hydroxymethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.00067
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-cyanophenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0017
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-cyanophenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.00028
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-fluorophenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0005
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-fluorophenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0018
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-hydroxyphenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0071
(2R,4R)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-hydroxyphenoxy)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0036
(2R,4R)-4-(azidomethyl)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
HO-1
0.038
(2R,4R)-4-(azidomethyl)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
HO-2
0.1
(2R,4R)-4-[((4-adamantan-1-yl)phenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1; HO-2
0.0014
(2R,4R)-4-[(4-aminophenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane dihydrochloride
-
HO-1
0.013
(2R,4R)-4-[(4-aminophenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane dihydrochloride
-
HO-2
0.0035
(2R,4R)-4-[(4-bromophenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.022
(2R,4R)-4-[(4-bromophenoxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.002
(2R,4R)-4-[(biphenyl-4-yloxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.043
(2R,4R)-4-[(biphenyl-4-yloxy)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0026
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)-methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.0026 mM
0.0021
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethyl)pyridin-2-ylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.016
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethyl)pyridin-2-ylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
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
-
-
0.0021
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane
P09601
pH and temperature not specified in the publication
0.0007
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-methoxyphenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0025
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-methoxyphenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.006
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-nitrophenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.019
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(4-nitrophenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.009
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(methylthio)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.019
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(methylthio)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0009
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(naphthalen-2-ylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.03
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(naphthalen-2-ylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.00103
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.034
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulfanyl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.025
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(pyridin-4-ylsulfanyl)methyl]-1,3-dioxolane dihydrochloride
-
HO-1
0.069
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(pyridin-4-ylsulfanyl)methyl]-1,3-dioxolane dihydrochloride
-
HO-2
0.0012
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-(fluoromethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0044
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-(fluoromethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0028
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-chlorophenylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.012
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-chlorophenylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0022
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-fluorophenylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.005
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-[(4-fluorophenylsulfanyl)methyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0035
(2R,4S)-4-(chloromethyl)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride monohydrate
-
HO-1
0.122
(2R,4S)-4-(chloromethyl)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride monohydrate
-
HO-2
0.006
(2R,4S)-4-[(2-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0123
(2R,4S)-4-[(2-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.005
(2R,4S)-4-[(3-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.022
(2R,4S)-4-[(3-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.0021
(2R,4S)-4-[(4-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-1
0.0024
(2R,4S)-4-[(4-bromophenylsulfanyl)methyl]-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane hydrochloride
-
HO-2
0.02
(2S,4R)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)-methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.02 mM
0.012
(2S,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-methyl-1,3-dioxolane
-
IC50: 0.012 mM
0.0019
1-((2-(2-(4-bromophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
IC50: 0.0019 mM
1.9
1-((2-(2-(4-bromophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
100
1-((2-(2-(4-bromophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
above, pH 7.4, 37C, brain isozyme HO-2
0.0043
1-((2-(2-(4-chlorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
IC50: 0.0043 mM
1.4
1-((2-(2-(4-chlorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
4.3
1-((2-(2-(4-chlorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
17.9
1-((2-(2-(4-chlorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
100
1-((2-(2-(4-chlorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
above, pH 7.4, 37C, brain isozyme HO-2
0.0038
1-((2-(2-(4-fluorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
IC50: 0.0038 mM
3.8
1-((2-(2-(4-fluorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
100
1-((2-(2-(4-fluorophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
above, pH 7.4, 37C, brain isozyme HO-2
0.0037
1-((2-(2-(4-iodophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
IC50: 0.0037 mM
3.7
1-((2-(2-(4-iodophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
100
1-((2-(2-(4-iodophenyl)ethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
above, pH 7.4, 37C, brain isozyme HO-2
0.0007
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
IC50: 0.0007 mM
0.7
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
100
1-((2-(2-phenylethyl)-1,3-dioxolan-2-yl)methyl)-1H-imidazole hydrochloride
-
above, pH 7.4, 37C, brain isozyme HO-2
0.00027
1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone
P09601
pH and temperature not specified in the publication
0.00011
1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanone hydrochloride
-
IC50: 0.00011 mM
0.11
1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanone hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
1.8
1-(1H-imidazol-1-yl)-4-(4-iodophenyl)-2-butanone hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.004
1-(1H-imidazol-1-yl)-4-phenyl-2-butanone hydrochloride
-
IC50: 0.004 mM
4
1-(1H-imidazol-1-yl)-4-phenyl-2-butanone hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
11.3
1-(1H-imidazol-1-yl)-4-phenyl-2-butanone hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.028
1-(2-phenoxyethyl)-1H-imidazole
-
pH 7.4, 37C
0.0025
1-(4-bromophenyl)-2-(1H-imidazol-1-yl)ethanone
-
pH 7.4, 37C
0.1
1-(4-bromophenyl)-2-[2-(1-methylethyl)-1H-imidazol-1-yl]ethanone
-
pH 7.4, 37C
0.007
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
P23711
-
0.0021
1-[4-(3-bromophenoxy)butyl]-1H-imidazole
-
pH 7.4, 37C
0.01
1-[6-(4-bromophenoxy)exyl]-1H-imidazole
-
pH 7.4, 37C
0.01
2-(1H-imidazol-1-yl)-1-(4-nitrophenyl)ethanol
-
pH 7.4, 37C
0.00014
2-[2-(4-bromophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
pH and temperature not specified in the publication
0.0005
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
pH and temperature not specified in the publication
0.004
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
IC50: 0.004 mM
0.0047
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3-dithiolane
-
IC50: 0.0047 mM
0.0014
2-[2-(4-fluorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
pH and temperature not specified in the publication
0.0062
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
P09601
pH and temperature not specified in the publication
0.00076
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl)methyl]1,3-dioxolane
P09601
pH and temperature not specified in the publication
0.0017
4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
IC50: 0.0017 mM
1.7
4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
9.5
4-(4-bromophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.0047
4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
IC50: 0.0047 mM
4.7
4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
43.1
4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
0.0027
4-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
IC50: 0.0027 mM
1.9
4-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
pH 7.4, 37C, brain isozyme HO-2
2.7
4-(4-fluorophenyl)-1-(1H-imidazol-1-yl)-2-butanone hydrochloride
-
pH 7.4, 37C, spleen isozyme HO-1
0.0025
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
-
-
0.0025
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
P09601
pH and temperature not specified in the publication
0.004
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
-
imidazole variant
0.089
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
-
1,2,3-triazolyl variant
0.00406
4-phenyl-1-(1H-imidazol-1-yl)-2-butanone
P09601
pH and temperature not specified in the publication
-
0.0053
azalanstat
-
IC50: 0.0053 mM
0.006
azalanstat
-
IC50: 0.006 mM
5.3
azalanstat
-
pH 7.4, 37C, spleen isozyme HO-1
24.5
azalanstat
-
pH 7.4, 37C, brain isozyme HO-2
0.0001
benzyl isocyanide
-
HO-2, inhibition of conversion of heme
0.00013
benzyl isocyanide
-
HO-1, inhibition of conversion of heme
0.005
benzyl isocyanide
-
HO-1, inhibition of conversion of verdoheme
0.017
DTE
-
isozyme HO-1, pH not specified in the publication, temperature not specified in the publication
1.2
DTE
-
isozyme HO-2, pH not specified in the publication, temperature not specified in the publication
0.00072
isopropyl isocyanide
-
HO-1, inhibition of conversion of heme
0.00025
n-butyl isocyanide
-
HO-1, inhibition of conversion of heme
0.00034
n-butyl isocyanide
-
HO-2, inhibition of conversion of heme
0.045
n-butyl isocyanide
-
HO-1, inhibition of conversion of verdoheme
0.00117
isopropyl isocyanide
-
HO-2, inhibition of conversion of heme
additional information
additional information
P09601
;
-
additional information
additional information
O70252, P14901
;
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00000625
-
activity in kidney microsomes, micromol bilirubin/min/mg
0.000015
-
cavernous tissue of sildenafil-treated rats
0.00004
-
spleen microsomes, pH 7.4, 37C
0.000175
-
spleen enzyme
0.00046
-
NADH-dependent heme degradation in heart mitochondria
0.0064
-
testis heme oxygenase-2, partialy purified
0.017
-
28000 Da recombinant tryptic fragment of heme oxygenase-2
0.024
-
recombinant C-terminal truncated heme oxygenase-1
0.05
-
hematoheme oxidation
0.052
-
protoheme oxidation
0.067
-
testicular heme oxygenase-2
0.0705
-
purified recombinant wild-type enzyme
0.072
-
37C, presence of Zn protoporphyrin IX
0.075 - 0.1
-
liver heme oxygenase from Co-treated animals, 2 fractions during purification
0.075
-
37C, presence of Zn protoporphyrin IX plus 0.2 mM Cd2+
0.095
-
testis heme oxygenase-2
0.101
-
purified recombinant HO-1 mutant R254K
0.104
-
liver heme oxygenase-1
0.11
-
liver heme oxygenase-1
0.113
-
spleen enzyme
0.138
-
liver heme oxygenase-1
0.142
-
37C, control
0.433
-
-
0.641
-
37C, presence of 0.2 mM Cd2+
4.712
-
HO-2
8.413
-
HO-1
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
the specific HO-1 activity increases from 0.82 to 24.8 U/mg during purification steps
additional information
-
-
additional information
P14901
-
additional information
-
transcription factor activation activity of recombinant wild-type and mutant enzymes, overview
additional information
P06762
activity in nonexposed control and SnPP-IX/CCl4-exposed liver tissue, overview
additional information
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6
Q4K657, Q4K7S1
PigA
6.75
O69002, Q88P48, Q9HWR4
PigA
6.75
Q88JR7
PigA
7
-
assay at
7.2 - 7.5
-
-
7.2
D9IWR7
-
7.25
-
HY1 and HO4
7.4
-
liver heme oxygenase-1 and testis heme oxygenase-2
7.4
-
assay at
7.4
-
assay at
7.6
-
assay at
7.6
Q5HSH8
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
O69002, Q88P48, Q9HWR4
high activity of PigA within this range; high activity of PigA within this range
6 - 9
Q4K657, Q4K7S1
high activity of PigA within this range
6 - 9
A4Y0Y8
high activity of PigA within this range
6 - 9
Q88JR7
high activity of PigA within this range
6 - 9
Q885D4, Q887K9
high activity of PigA within this range
6.5 - 7.9
-
pH 6.5: 63% activity, pH 7.9: 50% activity
7 - 9
-
binding capacity increases with the increasing pH from 7 to 9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
Q5HSH8
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
P06762
assay at
37
-
assay at
37
P14901
assay at
37
-
assay at
37
-
assay at
37
P14901
assay at
37
D9IWR7
-
37
P23711
assay at
45
O69002, Q88P48, Q9HWR4
above, PigA; above, PigA
45
Q4K657, Q4K7S1
above, PigA
45
A4Y0Y8
above, PigA
45
Q88JR7
above, PigA
45
Q885D4, Q887K9
above, PigA
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
no activity at 0C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
constitutive expression of HO-2
Manually annotated by BRENDA team
-
chromaffin cells
Manually annotated by BRENDA team
-
pulmonary
Manually annotated by BRENDA team
-
high HO-1 expression
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
isozyme HO-2
Manually annotated by BRENDA team
P09601
isozyme HO-2
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley, Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
adrenal medulla
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
-
bone marrow-derived, mature and immature
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
bone marrow-derived, mature and immature
-
Manually annotated by BRENDA team
-
aortic endothelial cell
Manually annotated by BRENDA team
-
HO-1 mRNA levels are 66% of those in liver
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
Hep-G2 cell line C34
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
Mus musculus C3H/HEN
-
-
-
Manually annotated by BRENDA team
P14901
overexpression of HO-1
Manually annotated by BRENDA team
Mus musculus C3H/HEN
-
overexpression of HO-1
-
Manually annotated by BRENDA team
-
a fibrosarcoma cell line
Manually annotated by BRENDA team
-
low HO-1 expression
Manually annotated by BRENDA team
-
human umbelical vein endothelial cells, expression analysis
Manually annotated by BRENDA team
-
i.e, human umbilical vein endothelial cells
Manually annotated by BRENDA team
-
i.e. human umbilical vein endothelial cell
Manually annotated by BRENDA team
-
immortalized hypothalamic neurons GT1-7
Manually annotated by BRENDA team
-
heme oxygenase-3, high level of heme oxygenase-2 in the outer medulla followed by inner medulla/papilla and cortex, heme oxygenase-1 is barely detectable in tissue from untreated animals but increases strongly in SnCl2 treated animals
Manually annotated by BRENDA team
-
renal epithelial cell culture
Manually annotated by BRENDA team
-
HO-1 and HO-2 contents, immunohistochemic analysis, overview
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
Manually annotated by BRENDA team
-
24 h after a CoCl2 injection heme-oxygenase-1 activity increases 13fold, enzyme may play a role in the liver oxidative-stress defence
Manually annotated by BRENDA team
P06762
parenchymal cells
Manually annotated by BRENDA team
-
enzyme is constitutively expressed in Kupffer cells, inducible in hepatocytes
Manually annotated by BRENDA team
-
HO-1 is expressed primarily in Kupffer cells, HCV-infected liver biopsies and core protein-expressing hepatocytes show diminished levels of heme oxygenase-1
Manually annotated by BRENDA team
Mus musculus C57/BL/6, Mus musculus C3H/HEN
-
-
-
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
-
increased expression on inflammation, particularly in infiltrating cells
Manually annotated by BRENDA team
-
immortalized hypothalamic neurons GT1-7
Manually annotated by BRENDA team
P06762
neutrophil HO-1 expression is similar in rats receiving burn injury alone compared with shams gavaged with saline, however, as compared with rats receiving EtOH intoxication, neutrophil HO-1 expression in burn rats is significantly decreased. Furthermore, a significant decrease in neutrophil HO-1 expression is observed in rats receiving a combined insult of EtOH intoxication and burn injury compared with rats receiving either sham or burn injury alone
Manually annotated by BRENDA team
-
a adrenal pheochromocytoma cell line
Manually annotated by BRENDA team
P06762
expression and immunohistochemic analysis in veno-occlusive priapism, overview
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
-
is slightly detectable in the abdominal skeletal muscle
Manually annotated by BRENDA team
-
increased expression on inflammation, particularly in infiltrating cells
Manually annotated by BRENDA team
-
heme oxygenase-1 and 2, relative ratio 5/1
Manually annotated by BRENDA team
-
highest expression of HO-1 mRNA levels in the spleen, 6.6fold of those in the liver
Manually annotated by BRENDA team
P09601
predominant expression of isozyme HO-1
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
-
-
-
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
P09601
isozyme HO-2
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
-
expression of HO-1 is tissue-specific, and there is a correspondence between levels of HO-1 mRNA and protein
Manually annotated by BRENDA team
additional information
-
in vivo, no HO-1 expression in extravillous trophoblasts and in nonproliferating, Kip2/p57-positive extravillous trophoblasts
Manually annotated by BRENDA team
additional information
D9IWR7
expressions of MsHO1 are higher in alfalfa stems and leaves than those in germinating seeds and roots, expression patterns, overview
Manually annotated by BRENDA team
additional information
-
isozyme HO-2 has a wider tissue distribution than isozyme HO-1
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
HY1, HO3, and HO4 are present as the processed mature protein in the plastid compartment
Manually annotated by BRENDA team
-
recombinant heme oxygenase-2 expressed in Escherichia coli
Manually annotated by BRENDA team
-
presence of the membrane-spanning region on HO-1 is required for efficient membrane incorporation, which is achieved after a 2 h preincubation period at room temperature
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley, Mus musculus C57BL/6
-
-
-
-
Manually annotated by BRENDA team
-
liver, 7% of microsomal activity
Manually annotated by BRENDA team
-
77% activity in inner membrane, specifically associated with complex I, NADH: ubiquinone oxidoreductase
Manually annotated by BRENDA team
-
in response to different stimuli, e.g. hypoxia by 3% oxygen or incubation with hemin or heme-hemopexin, HO-1 can migrate to the nucleus. Nuclear translocation is associated with truncation of the C-terminus of HO-1
Manually annotated by BRENDA team
-
in response to different stimuli, e.g. hypoxia by 3% oxygen or incubation with hemin or heme-hemopexin, HO-1 can migrate to the nucleus. Nuclear translocation is associated with truncation of the C-terminus of HO-1 by 52 amino acids, the C-terminal region of HO-1 inhibits the nuclear import
Manually annotated by BRENDA team
-
full-length HO-1 is an integral membrane protein
Manually annotated by BRENDA team
Mus musculus C57/BL/6
-
-
-
Manually annotated by BRENDA team
additional information
-
effect of nuclear localization of HO-1oncell viability
-
Manually annotated by BRENDA team
additional information
-
no mitochondrial localization of HY1, HO3, and HO4
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Corynebacterium diphtheriae (strain ATCC 700971 / NCTC 13129 / Biotype gravis)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Staphylococcus aureus (strain N315)
Synechocystis sp. (strain PCC 6803 / Kazusa)
Synechocystis sp. (strain PCC 6803 / Kazusa)
Synechocystis sp. (strain PCC 6803 / Kazusa)
Synechocystis sp. (strain PCC 6803 / Kazusa)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21600
-
calculated from amino acid sequence
673571
23450
-
MALDI-TOF
672143
26000
-
SDS-PAGE
673571
32000
-
SDS-PAGE
672651
33000
-
SDS-PAGE
672229
150000
-
gel filtration
438251
180000
-
gel filtration
438243
200000
-
gel filtration
288603, 438244
200000
-
gel filtration
438244
additional information
-
heme oxygenase consists of 3 components: a 22000 Da ferredoxin-like Fe/S cluster protein that can be replaced by ferredoxin, a 38000 Da protein that is inactivated by diethyldicarbonate, inactivation is blocked by heme, a 37000 Da protein with ferredoxin-linked cytochrome c reductase activity
438255
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 32000, SDS-PAGE
?
-
x * 32000, SDS-PAGE
?
-
x * 31000, SDS-PAGE
?
-
x * 30500, SDS-PAGE
?
-
x * 33000, SDS-PAGE
?
-
x * 33000, SDS-PAGE
?
-
x * 25000, recombinant enzyme, SDS-PAGE
?
-
x * 68000, possibly a trimer, SDS-PAGE
?
-
x * 24000, SDS-PAGE, deduced from amino acid sequence
?
-
x * 36000, heme oxygenase-2, SDS-PAGE
?
-
x * 36000, recombinant heme oxygenase-2, SDS-PAGE
?
-
x * 42000, heme oxygenase-2, SDS-PAGE
?
-
x * 30000, liver heme oxygenase-1, SDS-PAGE, x * 36000, testis heme oxygenase-2, SDS-PAGE
?
-
x * 30700, liver heme oxygenase-1, SDS-PAGE
?
-
x * 32000, kidney heme oxygenase, immunoblot
?
-
x * 23000, SDS-PAGE, recombinant enzyme, x * 21450, deduced from gene sequence
?
-
x * 25000, SDS-PAGE, recombinant enzyme
?
-
x * 32000, recombinant mutant R254K, SDS-PAGE
?
-
x * 28000, wild-type and mutant, SDS-PAGE
?
P09601
x * 32000, isozyme HO-1, x * 36500, isozyme HO-2
dimer
-
crystallization data
dimer
-
HugZ is a dimer in solution, that adopts a split-barrel fold. HugZ-hemin crystallizes as a trimer of dimers. Structure overview
homodimer
Q5HSH8
with a splitbarrel fold. One heme-binding site is at the dimer interface and another novel heme-binding site is found on the protein surface
monomer
-
1 * 27000, HY1, SDS-PAGE. HY1, HO3 and HO4, gel filtration
additional information
P30519
structure-function analysis
additional information
-
the C-terminal 23 amino acids are essential for maximal catalytic activity
additional information
-
structure comparisons, overview
additional information
H8XZ68
three-dimensional structure of BrHO1, analysis and comparison, overview
additional information
-
structure comparison of isozymes HO-1 and HO-2, overview. Both apo- and holoenzymes contain a hydrogen-bond network involving Asn210, Arg136, as well as a second level of residues, which includes Tyr58 and Tyr114 to stabilize the position of the catalytically critical Asp140 residue for HO-1 and Asp160 for HO-2. Structure-activity relationship analysis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
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
additional information
-
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
purified recombinant His-tagged enzyme complexed with hemin, hemin:ChuZ ratio of 2:1, microbatch method, mixing of 0..001 ml of 170 mg/ml ChuZ-hemin in 20 mM Tris-HCl, pH 8.0, and 5 mM sodium azide with 0.001 ml of reservoir solution consisting of 0.1 M MES, pH 6.5, 24% PEG400 v/v, and 0.1 M imidazole, X-ray diffraction structure determination and analysis at 2.5 A resolution
Q5HSH8
azide-bound Fe(II)-verdoheme-HmuO, 30C, a hanging drop vapor diffusion method, the reservoir solution containing 50 mM MES, pH 5.4, 2.3-2.5 M ammonium sulfate, 0.27 M sodium bromide, and 0.1% dioxane, X-ray diffraction structure determination and analysis at 3.0 A resolution
-
dioxygen bound form
-
DTT-bound forms of ferric heme-HO-1 complexes, X-ray diffraction structure analysis of crystal structures with PDB IDSs I9T and 3I9U, resolution is 1.5 A
-
ferric and ferrous forms of the heme complex
-
heme oxygenase HmuO in tertiary complex with reaction intermediate verdoheme and N3, X-ray diffraction structure determination and analysis at 1.7 resolution
-
wild-type and mutants D136E, D136N, D136A, D136F
-
sitting drop vapour diffusion method using 12-15% (w/v) polyethylene glycol 3350, 0.15-0.20 M magnesium formate, and 10-20 mM NAD
-
purified recombinant HugZ, hanging-drop vapour diffusion method, mixing of 0.001 ml of 25 mg/ml HugZ-hemin in 20 mM Tris, pH 8.0, 5 mM sodium azide, with 0.001 ml of reservoir solution consisting of 16% w/v PEG 3350, 3% Tacsimate, 0.1 M imidazole, pH 7.5, and 12% methanol, X-ray diffraction structure determination and analysis at 1.8-2.3 A resolution
-
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 4C, 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 4C, 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
P30519
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
P09601
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
P09601
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
-
crystal structure at 1.5 A resolution, comparison with heme oxygenase-1 from mammalian sources
-
in Fe(II), Fe(II)-CO and Fe(II)-NO state
-
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
-
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
-
heme oxygenase HO1 complexed with reaction intermediate verdoheme, X-ray diffraction structure determination and analysis at 2.2 A resolution
-
HO-1 in complex with (2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane to 2.70 A resolution, the heme and helix are shifted by ca. 0.8 A toward the alpha-meso carbon along the alpha-gamma axis of the heme
P23711
in complex with biliverdin-iron chelate
P06762
thiol-bound forms of ferric heme-HO-1 complexes, thiols are from DTT or DTE, X-ray diffraction structure analysis of crystal structures with PDB IDSs I9T and 3I9U, resolution is 2.15-2.25 A
P06762
truncated heme oxygenase-1, hanging-drop vapor diffusion, enzyme solution is mixed with an equal volume of each reservoir solution and equilibrated, crystals are obtained at 293 K, reservoir solution contains 4 M sodium formate, 18 mg/ml enzyme concentration in 50 mM potassium phosphate, pH 7.0, hexagonal rod-shaped crystals appear after 3 d, X-ray structure of heme oxygenase in complex with heme bound to azide at 1.9 A resolution
-
truncated, soluble hHO-1 variant, consisting of 233 amino acids, in complex with 4-phenyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone, sitting-drop vapor diffusion, room temperature, 0.412 mM heme-HO-1 complex in 20 mM potassium phosphate is mixed with inhibitor in a 1:3 molar ratio, the reservoir solution contains100 mM HEPES, pH 7.5, 2.00-2.28 M ammonium sulfate, and 0.8-1.1% 1,6-hexanediol, X-ray diffraction structure determination and analysis
-
in complex with heme
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 6.5
-
truncated HO-1 does not bind on the adsorbent at low pH 6 and 6.5
672651
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35
-
liver heme oxygenase-1: 65-70% activity after 10 min at 60C, testis heme oxygenase-2: 20% activity after 10 min at 60C
438254
50
-
complete loss of activity
438250
50
-
10 min, 80% loss of liver heme oxygenase-1 and testis heme oxygenase 2 activity
438256
50
-
-
438256
53
-
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
692400
60
-
5 min, complete loss of activity
438243
65
-
10 min, 30% loss of heme oxygenase-1 activity, 80% loss of heme oxygenase-2 activity
438254
90
-
15 min, 95% loss of activity, crude extract
438257
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
10-20% loss of activity upon thawing
-
50% loss of activity during one cycle of freezing and thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0C, 100 mM potassium phosphate buffer, pH 7.2, 4 days
-
4C, 20 mM potassium phosphate, pH 7.5, 0.2% Triton X-100, 20% glycerol, 2 d, 50% loss of activity
-
liquid nitrogen, 6 months, no loss of activity
-
-20C, 2 weeks
-
-30C, several weeks, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HY1, HO3, and HO4. HO3 and HO4 purified by cobalt affinity chromatography, to over 90% purity
-
Triton X-100 + cholate, DEAE-cellulose, hydroxyapatite, Sepharose CL-6B, hydroxyapatite
-
recombinant His-tagged HO1 from Escherichia coli by nickel affinity chromatography
H8XZ68
recombinant ChuZ from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
Q5HSH8
to apparent homogeneity
-
recombinant wild-type and His-tagged enzyme, ion-exchange, gel filtration
-
verdoheme-HmuO complex by anion exchange chromatography and gel filtration
-
Ni-NTA column chromatography and Resource Q column chromatography
-
DEAE-Sephacel, carboxymethyl-cellulose, hydroxyapatite, Superose 6/12
-
Sephadex G-75 gel filtration and DE-52 gel filtration
-
recombinant His6-tagged HugZ from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
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
-
recombinant GST-tagged wild-type and mutant HO-2 from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
P30519
truncated HO-1 and HO-2 lacking the 23 C-terminal residues, by gel filtration
-
Sephadex G25 gel filtration
-
recombinant enzyme, pure enzyme solution has a bright green colour
-
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 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
Q4K657, Q4K7S1
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
A4Y0Y8
recombinant GST-tagged PigA from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
Q88JR7
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
Q885D4, Q887K9
2 separate fractions after first DEAE-cellulose, hydroxyapatite, Sephadex G-150, DEAE-cellulose
-
DEAE-cellulose, Sephadex G-200
-
heme oxygenase-1; heme oxygenase-2
-
heme oxygenase-2
-
hydroxylapatite column chromatography and POROS-HQ column chromatography
-
ammonium sulfate, DEAE-cellulose, hydroxyapatite, Sephadex G-200
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HY1, HO3, and HO4 expressed without their predicted chloroplast transit peptides either using a tac promoter-driven N-terminal GST fusion expression system (HY1) or the pET vector system (HO3, HO4) using a T7-promoter and a His-tag fusion. Plasmids pGEX-mHY1, pET24a-mHO3 and pET24a-mHO4 expressed in Escherichia coli BL21 (DE3). Fluorescent protein expression in Nicotiana benthamiana by using Agrobacterium tumefaciens C58C1 pGV2260
-
DNA and amino acid sequence determination and analysis, genetic structure, phylogenetic analysis, functional expression of His-tagged HO1 in Escherichia coli
H8XZ68
gene chuZ, ChuZ is highly conserved in 32 clinical isolates. Genotyping, recombinant expression in Escherichia coli strain BL21(DE3)
Q5HSH8
expressed in Escherichia coli
-
expression of wild-type and His-tagged enzyme in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli BL21 (DE3) cells
-
expression of His6-tagged HugZ 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 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
-
overexpression of GST-tagged wild-type and mutant HO-2 in Escherichia coli strain BL21(DE3)
P30519
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
-
DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression of GFP-tagged HO1 targeted to chloroplasts. Expression of mature MsHO1 in Escherichia coli
D9IWR7
expression analysis
-
expression of the kappaB element of the proximal rat HO-1 gene promoter region, -284 to -275, a nuclear target for the NF-kappaB subunit p65/RelA, expression in in RAW264.7 monocytes fused to the luciferase gene. HO-1 promoter activity is induced by p65, an NF-kappaB subunit, which is also termed RelA, and which is a member of the Rel family of proteins and is activated in response to a variety of stimuli
-
overexpression of HO-1 in B16F10 melanoma cells
P14901
sense and antisense constructs, expression analysis in dendritic cells of different maturation levels, cobalt protoporphyrin leads to overexpression of HO-1, molecular mechanism, overview
-
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 bphOP, DNA and amino acid sequence, including promoter, determination and analysis, expression analysis, dependence of bphOP expression on RpoS
-
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)
Q4K657, Q4K7S1
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)
A4Y0Y8
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)
Q88JR7
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)
Q885D4, Q887K9
DNA and amino acid sequence determination of wild-type and mutant, full-length and truncated enzymes, expression of the N-terminus of the rat enzyme in human HEK-293 cells, and of FLAG-tagged inactive mutant H25A in 3T3 cells, nuclear translocation of enzyme mutants lacking the C-terminus and of mutant H25A, overview
-
expressed in Escherichia coli; expression in rat basophilic leukemia RBL-2H3 cells
-
expression analysis
-
expression of GST-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), transfection of wild-type HO-1 cDNA or intracellular delivery of pure HO-1 protein into cultured NIH 3T3 cells results in activation of a 15-kb HO-1 promoter independently of HO activity, expression of an catalytically inactive HO-1 also results in promoter activation, HO-1-mediated promoter activation is regulated via the distal enhancers E1 and E2
-
expression of the kappaB element of the proximal rat HO-1 gene promoter region, -284 to -275, a nuclear target for the NF-kappaB subunit p65/RelA, expressionin in RAW264.7 monocytes fused to the luciferase gene
-
expression of truncated heme oxygenase-1 in Escherichia coli
-
expression of wild-type heme oxygenase-1 and 2 and heme oxygenase-2 C264A/C281A double mutant in Escherichia coli
-
semiquantitative RT-PCR expression analysis of HO-1
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HO1 is induced by several stress conditions, e.g. osmotic and salinity stresses, cadmium exposure, H2O2, and hemin treatments
H8XZ68
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
-
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
-
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
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HO-1 protein expression is strongly induced 24 h after DOX addition in the HTR-8/SVneo cell line
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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
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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
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HO-1 activity is upregulated in response to several therapeutic treatments and is implicated in promoting tumour growth
P09601
HO-1 expression is chemically induced by cobalt protoporphyrin-IX in HEK293 T-RExTM Nox4 cells resulting in downregulation of NADPH oxidase Nox4 activity
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MsHO1 gene expression and protein level are induced significantly by some pro-oxidant compounds, including hemin and nitric oxide donor sodium nitroprusside
D9IWR7
HO-1 induction after hemoglobin treatment is decreased by about half by MEK inhibitors U0126 and SL327, and is completely prevented by the direct ERK inhibitor FR180204
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HO-1 induction by hemoglobin. In cultures treated with hemoglobin plus dimethylsulfoxide vehicle for 4 h, which is a time point prior to the onset of neuronal lysis, HO-1 expression is increased 2.2fold over control cultures treated with vehicle only
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HO-1 is induced by inflammation associated both with an anti-inflammatory response and with mitochondrial biogenesis
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HO-1 is induced by inflammation associated both with an anti-inflammatory response and with mitochondrial biogenesis
Mus musculus C57/BL/6
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pretreatment with hemoglobin induces HO-1 and significantly reduces systemic inflammations associated with plasma concentrations of TNFalpha levels due to intestinal ischemia/reperfusion injury
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renal HO-1 is induced by angiotensin II, ANG II, when given in high doses
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renal HO-1 is induced by angiotensin II, ANG II, when given in high doses
Rattus norvegicus Sprague-Dawley
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D136A
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reduced heme degradation activity, formation of ferryl heme
D136E
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enzymic activity similar to wild-type
D136F
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reduced heme degradation activity, formation of ferryl heme
D136N
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enzymic activity similar to wild-type
H20A
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capable of NADPH dependent hydroxylation of heme to alpha-mesohydroxyheme in contrast to human H25A heme oxygenase-1 mutant, ability to catalyze the conversion of verdoheme to biliverdin is rescued by imidazole titration
H193N
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inactive enzyme
H73A
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no spectrum compared with native ChuS
H245A
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
H245A/R166A
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site-directed mutagenesis, inactive mutant
H245N/R166A
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site-directed mutagenesis, inactive mutant
H245Q
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
R166A
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site-directed mutagenesis, the mutation completely abolished the HO activity of HugZ
C127A
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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
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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
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21% activity compared to the wild type enzyme
D140A
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abolished activity, retains the unusual wild-type azide complex spin/orbital ground state
D140A
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exhibits resolved and relaxed 2,4-dimethyldeuterohemin resonances at low pH and at high pH
D140H
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0.5% activity compared to the wild type enzyme
D140K
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7.1% activity compared to the wild type enzyme
E29K
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26% activity compared to the wild type enzyme
G139A
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retains about 60% of the wild type HO activity
G143H
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the replacement of Gly143 with His leads to the formation of a bis-histidine complex
H132A
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heme oxygenase-1, 40-50% of wild-type activity
H132G
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heme oxygenase-1, 40-50% of wild-type activity
H132S
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heme oxygenase-1, 20% of wild-type activity
H20A
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H25A
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about 10% of wild-type activity, binding activity to heme similar to wild-type
H25A
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mutation leads to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Enzymatic activity is reduced by 90.5%. By supplementing imidazole, the HO-1 activity is restored approximately 87.5% to its normal level
K18A
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114% activity compared to the wild type enzyme
K18A/R183E
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2% activity compared to the wild type enzyme
K18A/Y134F/R183E
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2% activity compared to the wild type enzyme
K18E
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92% activity compared to the wild type enzyme
K18E/E29K/R183E
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1.2% act