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Literature summary 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

EC Number Application Comment Organism
2.1.1.28 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)

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

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.1.28 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
2.1.1.28 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
2.1.1.28 1,2,3,4-tetrahydroisoquinoline a nonselective inhibitor Homo sapiens
2.1.1.28 1,2,3,4-tetrahydroisoquinoline a nonselective inhibitor Rattus norvegicus
2.1.1.28 7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Homo sapiens
2.1.1.28 7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Rattus norvegicus
2.1.1.28 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
2.1.1.28 7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Rattus norvegicus
2.1.1.28 7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Homo sapiens
2.1.1.28 7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Rattus norvegicus
2.1.1.28 7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Homo sapiens
2.1.1.28 7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Rattus norvegicus
2.1.1.28 7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Homo sapiens
2.1.1.28 7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Rattus norvegicus
2.1.1.28 7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Homo sapiens
2.1.1.28 7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Rattus norvegicus
2.1.1.28 7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Homo sapiens
2.1.1.28 7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride
-
 Rattus norvegicus
2.1.1.28 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
2.1.1.28 additional information inhibitor docking studies, molecular modelling Rattus norvegicus

Natural Substrates/ Products (Substrates)

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

Organism

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

Substrates and Products (Substrate)

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

Synonyms

EC Number Synonyms Comment Organism
2.1.1.28 PNMT
-
 Homo sapiens
2.1.1.28 PNMT
-
 Rattus norvegicus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.1.1.28 25
-
 assay at, docking to alpha-adenosyl receptor Rattus norvegicus
2.1.1.28 37
-
 assay at, docking to inhibitors Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.1.1.28 7.7
-
 assay at, docking to alpha-adenosyl receptor Rattus norvegicus
2.1.1.28 8
-
 assay at, docking to inhibitors Homo sapiens

Cofactor

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

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.1.1.28 0.00022
-
 7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline
-
 Homo sapiens
2.1.1.28 0.00022
-
 7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline pH 8.0, 37°C Homo sapiens
2.1.1.28 0.00022
-
 7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline pH 7.7, 25°C Rattus norvegicus
2.1.1.28 0.00049
-
 1,2,3,4-tetrahydrobenz[h]isoquinoline pH 8.0, 37°C Homo sapiens
2.1.1.28 0.00049
-
 1,2,3,4-tetrahydrobenz[h]isoquinoline pH 7.7, 25°C Rattus norvegicus
2.1.1.28 0.0009
-
 7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 0.00091
-
 7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 0.0021
-
 7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 0.0023
-
 7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens
2.1.1.28 0.0058
-
 1,2,3,4-tetrahydroisoquinoline pH 8.0, 37°C Homo sapiens
2.1.1.28 0.0058
-
 1,2,3,4-tetrahydroisoquinoline pH 7.7, 25°C Rattus norvegicus
2.1.1.28 0.033
-
 7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline
-
 Homo sapiens