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Literature summary for 1.14.14.18 extracted from

  • Rahman, M.N.; Vukomanovic, D.; Vlahakis, J.Z.; Szarek, W.A.; Nakatsu, K.; Jia, Z.
    Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds (2013), J. R. Soc. Interface, 10, 20120697.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development heme oxygenase has cytoprotective properties and may play a role in several disease states, making it an interesting therapeutic target Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane
-
Homo sapiens
(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulphanyl)methyl]-1,3-dioxolane
-
Homo sapiens
1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone
-
Homo sapiens
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
-
Homo sapiens
2-[2-(4-bromophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
Homo sapiens
2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
Homo sapiens
2-[2-(4-fluorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
Homo sapiens
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
-
Homo sapiens
2-[2-phenylethyl]-2-[(1H-imidazol-1-yl)methyl]1,3-dioxolane
-
Homo sapiens
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
-
Homo sapiens
4-phenyl-1-(1H-imidazol-1-yl)-2-butanone
-
Homo sapiens
azalanstat
-
Homo sapiens
chromium protoporphyrin
-
Homo sapiens
additional information 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 Homo sapiens
pegylated zinc protoporphyrin inhibition of isozyme HO-1 Homo sapiens
tin protoporphyrin
-
Homo sapiens
zinc protoporphyrin low inhibition Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
32000
-
x * 32000, isozyme HO-1 Homo sapiens
36500
-
x * 36500, isozyme HO-2 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
heme + 3 AH2 + 3 O2 Homo sapiens
-
biliverdin + Fe2+ + CO + 3 A + 3 H2O
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P09601 inducible isozyme HO-1
-
Homo sapiens P30519 constitutive isozyme HO-2
-

Source Tissue

Source Tissue Comment Organism Textmining
brain isozyme HO-2 Homo sapiens
-
breast cancer cell
-
Homo sapiens
-
lymph node cancer cell
-
Homo sapiens
-
additional information isozyme HO-2 has a wider tissue distribution than isozyme HO-1 Homo sapiens
-
pancreatic cancer cell
-
Homo sapiens
-
prostate cancer cell
-
Homo sapiens
-
spleen
-
Homo sapiens
-
spleen predominant expression of isozyme HO-1 Homo sapiens
-
testis isozyme HO-2 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
heme + 3 AH2 + 3 O2
-
Homo sapiens biliverdin + Fe2+ + CO + 3 A + 3 H2O
-
?

Subunits

Subunits Comment Organism
? x * 32000, isozyme HO-1 Homo sapiens
? x * 36500, isozyme HO-2 Homo sapiens
More 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 Homo sapiens

Synonyms

Synonyms Comment Organism
heme oxygenase-1
-
Homo sapiens
HO-1
-
Homo sapiens
HO-2
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00014
-
pH and temperature not specified in the publication Homo sapiens 2-[2-(4-bromophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
0.00027
-
pH and temperature not specified in the publication Homo sapiens 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone
0.0005
-
pH and temperature not specified in the publication Homo sapiens 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
0.00076
-
pH and temperature not specified in the publication Homo sapiens 2-[2-phenylethyl]-2-[(1H-imidazol-1-yl)methyl]1,3-dioxolane
0.0014
-
pH and temperature not specified in the publication Homo sapiens 2-[2-(4-fluorophenyl)ethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane
0.0021
-
pH and temperature not specified in the publication Homo sapiens (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane
0.0025
-
pH and temperature not specified in the publication Homo sapiens 4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
0.00406
-
pH and temperature not specified in the publication Homo sapiens 4-phenyl-1-(1H-imidazol-1-yl)-2-butanone
0.0062
-
pH and temperature not specified in the publication Homo sapiens 2-[2-phenylethyl]-2-[(1H-imidazol-1-yl) methyl]-1,3-dioxolane

Expression

Organism Comment Expression
Homo sapiens HO-1 activity is upregulated in response to several therapeutic treatments and is implicated in promoting tumour growth up

General Information

General Information Comment Organism
additional information structure-activity relationship analysis Homo sapiens
physiological function 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 Homo sapiens
physiological function 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 Homo sapiens