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Literature summary for 2.1.1.28 extracted from

  • Grunewald, G.L.; Seim, M.R.; Regier, R.C.; Criscione, K.R.
    Exploring the active site of phenylethanolamine N-methyltransferase with 1,2,3,4-tetrahydrobenz[h]isoquinoline inhibitors (2007), Bioorg. Med. Chem., 15, 1298-1310.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
additional information a potent inhibitor of phenylethanolamine N-methyltransferase, which exhibits minimal affinity for the alpha2-adrenoceptor and is able to cross the brain-blood-barrier, would be a useful pharmacological tool for defining the role of epinephrine in the central nervous systhem. Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Eschrischia coli Homo sapiens
expression of C-terminally His6-tagged wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1,2,3,4-tetrahydrobenz[h]isoquinoline the inhibitor forms hydrophobic interactions with Val53, Met258, Val272, and Val269 in the PNMT active site, binding site structure, overview Homo sapiens
1,2,3,4-tetrahydrobenz[h]isoquinoline the inhibitor forms hydrophobic interactions with Val53, Met258, Val272, and Val269 in the PNMT active site, binding site structure, overview Rattus norvegicus
1,2,3,4-tetrahydroisoquinoline a nonselective inhibitor Homo sapiens
1,2,3,4-tetrahydroisoquinoline a nonselective inhibitor Rattus norvegicus
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Homo sapiens
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Rattus norvegicus
7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline 7-bromo-1,2,3,4-tetrahydroben[h]isoquinoline is 2fold more potent as an inhibitor of phenylethanolamine N-methyltransferase than 1,2,3,4-tetrahydroben[h]isoquinoline. Homo sapiens
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Rattus norvegicus
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Homo sapiens
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Rattus norvegicus
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Homo sapiens
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Rattus norvegicus
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Homo sapiens
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Rattus norvegicus
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Homo sapiens
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Rattus norvegicus
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Homo sapiens
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
Rattus norvegicus
additional information inhibitor docking studies, molecular modelling; the addition of a 7-substituent (NO2, SO2NH2, OMe, OH, or CN) to 1,2,3,4-tetrahydroben[h]isoquinoline does not lead to an increase in phenylethanolamine N-methyltransferase inhibitory potency. Homo sapiens
additional information inhibitor docking studies, molecular modelling Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Rattus norvegicus the enzyme binds to the alpha-adrenoreceptor ?
-
?
S-adenosyl-L-methionine + norepinephrine Homo sapiens last step in biosynthesis of epinephrine S-adenosyl-L-homocysteine + epinephrine
-
?
S-adenosyl-L-methionine + norepinephrine Rattus norvegicus last step in biosynthesis of epinephrine S-adenosyl-L-homocysteine + epinephrine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Rattus norvegicus
-
male Spargue-Dawley rats
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the enzyme binds to the alpha-adrenoreceptor Rattus norvegicus ?
-
?
S-adenosyl-L-methionine + norepinephrine
-
Homo sapiens S-adenosyl-L-homocysteine + epinephrine
-
?
S-adenosyl-L-methionine + norepinephrine
-
Rattus norvegicus S-adenosyl-L-homocysteine + epinephrine
-
?
S-adenosyl-L-methionine + norepinephrine last step in biosynthesis of epinephrine Homo sapiens S-adenosyl-L-homocysteine + epinephrine
-
?
S-adenosyl-L-methionine + norepinephrine last step in biosynthesis of epinephrine Rattus norvegicus S-adenosyl-L-homocysteine + epinephrine
-
?

Synonyms

Synonyms Comment Organism
PNMT
-
Homo sapiens
PNMT
-
Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at, docking to alpha-adenosyl receptor Rattus norvegicus
37
-
assay at, docking to inhibitors Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.7
-
assay at, docking to alpha-adenosyl receptor Rattus norvegicus
8
-
assay at, docking to inhibitors Homo sapiens

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine
-
Homo sapiens
S-adenosyl-L-methionine
-
Rattus norvegicus

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00022
-
7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline
-
Homo sapiens
0.00022
-
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline pH 8.0, 37°C Homo sapiens
0.00022
-
7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline pH 7.7, 25°C Rattus norvegicus
0.00049
-
1,2,3,4-tetrahydrobenz[h]isoquinoline pH 8.0, 37°C Homo sapiens
0.00049
-
1,2,3,4-tetrahydrobenz[h]isoquinoline pH 7.7, 25°C Rattus norvegicus
0.0009
-
7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
0.00091
-
7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
0.0021
-
7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
0.0023
-
7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens
0.0058
-
1,2,3,4-tetrahydroisoquinoline pH 8.0, 37°C Homo sapiens
0.0058
-
1,2,3,4-tetrahydroisoquinoline pH 7.7, 25°C Rattus norvegicus
0.033
-
7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
Homo sapiens