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Literature summary for 1.14.14.18 extracted from

  • Rahman, M.N.; Vlahakis, J.Z.; Roman, G.; Vukomanovic, D.; Szarek, W.A.; Nakatsu, K.; Jia, Z.
    Structural characterization of human heme oxygenase-1 in complex with azole-based inhibitors (2010), J. Inorg. Biochem., 104, 324-330.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
-
Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Rattus norvegicus
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 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
-
Rattus norvegicus
(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
(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 Homo sapiens
(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; azalanstat, potent inhibitor of HO Rattus norvegicus
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
-
Homo sapiens
1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
-
Rattus norvegicus
4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
-
Homo sapiens
ketoconazole
-
Rattus norvegicus
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 Homo sapiens
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 Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
Rattus norvegicus
-
-

Organism

Organism UniProt Comment Textmining
Homo sapiens P09601
-
-
Rattus norvegicus P06762
-
-
Rattus norvegicus P23711
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Rattus norvegicus
-
spleen
-
Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
heme + electron donor + O2
-
Homo sapiens biliverdin + Fe2+ + CO + oxidized electron donor + H2O
-
?
heme + electron donor + O2
-
Rattus norvegicus biliverdin + Fe2+ + CO + oxidized electron donor + H2O
-
?

Synonyms

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

Cofactor

Cofactor Comment Organism Structure
heme
-
Homo sapiens
heme
-
Rattus norvegicus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00006
-
substitution of the chlorophenyl group in the western region to a iodophenyl group Rattus norvegicus (2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
0.00014
-
substitution of the chlorophenyl group in the western region to a bromophenyl group Rattus norvegicus (2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
0.0014
-
substitution of the chlorophenyl group in the western region to a fluorophenyl group Rattus norvegicus (2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
0.0021
-
-
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
-
-
Homo sapiens 4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
0.004
-
-
Rattus norvegicus (2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
0.004
-
imidazole variant Homo sapiens 4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one
0.0062
-
substitution of the chlorophenyl group in the western region to a phenyl group Rattus norvegicus (2-[2-(4-chlorophenyl)ethyl]-2-[1H-imidazol-1-yl)methyl]-1,3-dioxolane
0.007
-
-
Rattus norvegicus 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethanone
0.089
-
1,2,3-triazolyl variant Homo sapiens 4-phenyl-1-(1,2,4-1H-triazol-1-yl)butan-2-one