Information on EC 2.1.1.28 - phenylethanolamine N-methyltransferase and Organism(s) Homo sapiens and UniProt Accession P11086

-

672011, 675288

hPNMT

-

672345, 718776, 720467

methyltransferase, noradrenaline N-

-

NMT

-

noradrenalin methyltransferase

-

noradrenalin N-methyltransferase

-

noradrenaline N-methyltransferase

-

norepinephrin N-methyltransferase

-

norepinephrine methyltransferase

-

norepinephrine N-methyltransferase

-

phenethanolamine methyltransferase

-

phenethanolamine N-methyltransferase

-

PNMT

S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine

to elucidate the detailed mechanism of enzymatic catalysis of PNMT, combined quantum-mechanical/molecular-mechanical (QM/MM) calculations are performed. The calculation results reveal that this catalysis contains three elementary steps: the deprotonation of protonated norepinphrine, the methyl transferring step and deprotonation of the methylated norepinphrine. The methyl transferring step is proved to be the rate-determining step undergoing a SN2 mechanism with an energy barrier of 16.4 kcal/mol

-

catecholamine biosynthesis

methyl group transfer

-

BRENDA

KEGG

Tyrosine metabolism

-

-, -

S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase

Acts on various phenylethanolamines; converts noradrenaline into adrenaline.

9037-68-7

-

3-trifluoromethylphenylethanolamine + S-adenosyl-L-methionine

?

-

-

?

3-trifluoromethylphenylethanolamine + S-adenosyl-L-methionine

N-methyl-3-trifluoromethylphenylethanolamine + S-adenosyl-L-homocysteine

-

-

?

anti-9-amino-6-(trifluoromethyl)benzonorbornene + S-adenosyl-L-methionine

?

-

-

?

cis-(1R,2S)-2-amino-1-tetralol + S-adenosyl-L-methionine

cis-(1R,2S)-2-methylamino-1-tetralol + S-adenosyl-L-homocysteine

-

-

?

octopamine + S-adenosyl-L-methionine

N-methyloctopamine + S-adenosyl-L-homocysteine

phenylethanolamine + S-adenosyl-L-methionine

N-methylphenylethanolamine + S-adenosyl-L-homocysteine

S-adenosyl-L-methionine + 4-aminomethyl-1,2,3,4-tetrahydroisoquinoline

S-adenosyl-L-homocysteine + ?

-

-

?

S-adenosyl-L-methionine + phenylethanolamine

S-adenosyl-L-homocysteine + N-methylphenylethanolamine

9-methylnorharman + S-adenosyl-L-methionine

? + S-adenosyl-L-homocysteine

norepinephrine + S-adenosyl-L-methionine

epinephrine + S-adenosyl-L-homocysteine

-

-

?

S-adenosyl-L-methionine + noradrenaline

S-adenosyl-L-homocysteine + epinephrine

-

718999, 720467

-

?

S-adenosyl-L-methionine + norepinephrine

S-adenosyl-L-homocysteine + epinephrine

S-adenosyl-L-methionine + phenylethanolamine

S-adenosyl-L-homocysteine + N-methylphenylethanolamine

-

672345, 699423, 718693

-

?

additional information

?

-

4 entries

9-methylnorharman + S-adenosyl-L-methionine

? + S-adenosyl-L-homocysteine

-

PNMT catalyzes the 2N-methylation of beta-carbolines, forming 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin MPP+

-

?

S-adenosyl-L-methionine + norepinephrine

S-adenosyl-L-homocysteine + epinephrine

S-adenosyl-L-methionine + phenylethanolamine

S-adenosyl-L-homocysteine + N-methylphenylethanolamine

-

-

?

additional information

?

-

-

the enzyme is involved in norepinephrine pathways

-

?

S-adenosyl-L-methionine

-

672557, 696719, 699423

2,3-dichloro-alpha-methylbenzylamine

-

3,4-dichloroamphetamine

-

3-fluoromethyl-7-(2,2,2-trifluoroethylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-fluoromethyl-7-(3,3,3-trifluoropropylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-fluoromethyl-7-(4,4,4-trifluorobutylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-fluoromethyl-7-(4-chlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-fluoromethyl-7-propylsulfonyl-1,2,3,4-tetrahydroisoquinoline

-

7,8-dichloro-1,2,3,4-tetrahydroisoquinoline

i.e. SK&F 64139

7-(3-methoxypropylsulfonyl)-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

7-butylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

7-ethylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

7-iodo-1,2,3,4-tetrahydroisoquinoline

7-nitro-1,2,3,4-tetrahydroisoquinoline

7-sulfonamido-1,2,3,4-tetrahydroisoquinoline

-

8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine

LY134046

2,3,4,5-tetrahydro-1H-2-benzyzepine derivate with two chloro substituents on the aromatic ring. Is able to cross the blood-brain barrier.

SKF 29661

SKF 64139

1,2,3,4-tetrahydroisoquinoline derivate with two chloro substituents on the aromatic ring. Is able to cross the blood-brain barrier.

trans-(1S,2S)-2-amino-1-tetralol

-

(6R)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

(6R)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

(6S)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

(6S)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol

-

(R)-7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline

-

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

1,2,3,4-tetrahydroisoquinoline

1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

1,4-diaminonaphthalene-2,6-disulfonic acid

-

1-(2,3-dichlorophenyl)ethanamine

-

1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)ethanone

-

1-aminoisoquinoline

-

Kd: 14 microM

1-phenylmethanamine

-

1-thiophen-2-ylmethanamine

-

1-thiophen-3-ylmethanamine

-

2-amino-1-methylbenzimidazole

-

Kd: 4.6 microM

2-amino-4(7)-hydroxy-benzimidazole

-

Kd: 20 microM

2-amino-5(6)-chloro-7(4)-hydroxy-benzimidazole

-

Kd: 14 microM

2-amino-5(6)-chloro-benzimidazole

-

Kd: 1.8 microM

2-amino-5(6)-fluoro-benzimidazole

-

Kd: 7.2 microM

2-aminobenzimidazole

-

Kd: 6.3 microM

2-bromo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

2-bromo-6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

2-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

2-phenylethanamine

-

2-Phenylethylamine

-

2-thiophen-2-ylethanamine

-

3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

very high selectivity

3-(fluoromethyl)-7-(thiomorpholin-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-(fluoromethyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

high selectivity

3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

very high selectivity

3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

3-(trifluoromethyl)-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine

-

3-butyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-(ethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-(propylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

3-difluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

3-ethyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

moderate selectivity

3-ethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

moderate selectivity

3-ethyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

moderate selectivity

3-fluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline

-

3-hydroxyethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline

-

3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

3-hydroxymethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

high selectivity

3-hydroxypropyl-7-bromo-1,2,3,4-tetrahydroisoquinoline

-

extension of the 3-hydroxyalkyl chain by just one carbon results in a significant loss in phenylethanolamine N-methyltransferse inhibitory potency

3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

3-isopropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

3-methyl-1,2,3,4-tetrahydroisoquinoline

3-methyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

high selectivity

3-methyl-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine

-

3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

3-methyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

high selectivity

3-Phenylpropylamine

-

3-propyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

high selectivity

3-propyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

moderate selectivity

3-thienylmethylamine

-

inhibits the enzyme and is selective toward the alpha2-adrenoceptor

3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines

-

several 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines and some enantiomers of 3-trifuoromethyl-1,2,3,4-tetrahydroisoquinolines. For the phenylethanolamine N-methyltransferase inhibitory potency of different 3-trifuoromethyl-1,2,3,4-tetrahydroisoquinolines, compounds bearing a lipophilic 7-substituent show higher potency than compounds bearing a hydrophilic 7-substituent. Comparison to the inhibitory activity of the entantiomers of the most potent racemates show that the R-enantiomers are approximately 4fold as potent as their corresponding S-enantiomers.

672582

-

4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide

-

4-(benzo[d][1,3]dioxol-5-ylamino)-4-oxobutanoic acid

-

4-bromo-1H-imidazole

-

Kd: 170 microM

4-oxo-1,4-dihydroquinoline-3,7-dicarboxylic acid

-

4-quinolinol

-

Kd: 690 microM

5-chlorobenzimidazole

-

Kd: 97 microM

6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

6-Aminoquinoline

-

Kd: 380 microM

6-Chloropurine

-

Kd: 140 microM

6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

7,8-dichloro-1,2,3,4-tetrahydroisoquinoline

-

661339, 696719

7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

7-(N-butylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride

-

7-aminosulfonyl-1,2,3,4-tetrahydroisoquinoline

-

i.e. SK&F 29661

7-aminosulfonyl-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

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.

7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride

-

7-bromo-1,2,3,4-tetrahydroisoquinoline

7-bromo-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline

-

high selectivity

7-bromo-3-butyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-bromo-3-ethyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-bromo-3-hydroxyethyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline

-

moderate selectivity

7-bromo-3-hydroxypropyl-1,2,3,4-tetrahydroisoquinoline

-

little selcetivity

7-bromo-3-isopropyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-bromo-3-methyl-1,2,3,4-tetrahydroisoquinoline

7-bromo-3-pentyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-bromo-3-propyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride

-

7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride

-

7-iodo-1,2,3,4-tetrahydroisoquinoline

-

7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride

-

7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline hydrochloride

-

7-nitro-1,2,3,4-tetrahydroisoquinoline

7-nitro-3-pentyl-1,2,3,4-tetrahydroisoquinoline

-

little selectivity

7-nitro-3-propyl-1,2,3,4-tetrahydroisoquinoline

-

moderate selectivity

7-sulfonamido-1,2,3,4-tetrahydroisoquinoline

-

8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine

-

adenine

-

Kd: 180 microM

benzylamine

-

LY134046

-

selective inhibitor, IC50: 0.0019 mM

N-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

661339, 699423

N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

R-(+)-7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline

-

SK&F 29661

-

additional information

6 entries

-

0.00054 - 0.055

3-trifluoromethylphenylethanolamine

0.047

4-aminomethyl-1,2,3,4-tetrahydroisoquinoline

-

0.0015 - 0.025

anti-9-amino-6-(trifluoromethyl)benzonorbornene

0.0053

cis-(1R,2S)-2-amino-1-tetralol

wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30°C.

0.0055

octopamine

0.07 - 2.05

phenylethanolamine

14 entries

0.0012 - 0.045

S-adenosyl-L-methionine

18 entries

0.0184

norepinephrine

-

wild-type enzyme

0.095

phenylethanolamine

-

purified in the absence of reducing agent, dimer, His-tagged

0.0035 - 0.0194

S-adenosyl-L-methionine

additional information

-

Km-value of mutant enzymes

-

0.001 - 0.0083

3-trifluoromethylphenylethanolamine

0.0043 - 0.0062

anti-9-amino-6-(trifluoromethyl)benzonorbornene

0.0048

cis-(1R,2S)-2-amino-1-tetralol

wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30°C.

0.02 - 0.021

octopamine

0.00017 - 0.0483

phenylethanolamine

7 entries

0.0017 - 0.0658

S-adenosyl-L-methionine

6 entries

0.045

phenylethanolamine

-

purified in the absence of reducing agent, dimer, His-tagged

15.5

3-trifluoromethylphenylethanolamine

pH 8.0, 30°C

3.67

octopamine

pH 8.0, 30°C

0.467

phenylethanolamine

pH 8.0, 30°C

0.000072 - 0.00133

2,3-dichloro-alpha-methylbenzylamine

0.00227 - 0.0148

3,4-dichloroamphetamine

0.0014

3-fluoromethyl-7-(2,2,2-trifluoroethylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.0013

3-fluoromethyl-7-(3,3,3-trifluoropropylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.067

3-fluoromethyl-7-(4,4,4-trifluorobutylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.032

3-fluoromethyl-7-(4-chlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.0024

3-fluoromethyl-7-propylsulfonyl-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.0000016

7,8-dichloro-1,2,3,4-tetrahydroisoquinoline

pH 8.0, 30°C

0.072

7-(3-methoxypropylsulfonyl)-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamnie as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.018

7-butylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.014

7-ethylsulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline

inhibition constants are determine using four concentrations of phenylethanolamnie as the variable substrate and three concentrations of inhibitor with a radiochemical assay.

0.00037

7-iodo-1,2,3,4-tetrahydroisoquinoline

-

0.00004 - 0.067

7-nitro-1,2,3,4-tetrahydroisoquinoline

9 entries

0.00056

7-sulfonamido-1,2,3,4-tetrahydroisoquinoline

-

0.0000044 - 0.00026

8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine

0.0000044 - 0.00312

LY134046

5 entries

0.000057 - 0.321

SKF 29661

8 entries

0.00000155 - 0.001375

SKF 64139

5 entries

0.0021

trans-(1S,2S)-2-amino-1-tetralol

wild type enzyme, assay mixture consists of 25 microl of 0.5 M phosphate buffer (pH 8.0), 5 microl of [methyl-3H]S-adenosyl-L-methionine containing approximately 2.5 X 10 00000 dpm, varying amounts of phenylethanolamine and unlabeled S-adenosyl-L-methionine, 20 microl enzyme and water at 30°C. The concentration of S-adenosyl-L-methionine is fixed on 5 microM.

0.0096

(6R)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

R-isomer, pH 8.0, 37°C

0.15

(6R)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

R-isomer, pH 8.0, 37°C

0.00031

(6S)-6-methyl-2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

S-isomer, pH 8.0, 37°C

0.0033

(6S)-6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

S-isomer, pH 8.0, 37°C

0.000017 - 0.000145

(7-nitro-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol

0.00049

1,2,3,4-tetrahydrobenz[h]isoquinoline

-

pH 8.0, 37°C

0.0058

1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

672557, 696719

0.00012 - 0.0069

1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

0.00009

1-(2,3-dichlorophenyl)ethanamine

-

pH 8.0

0.061

1-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)ethanone

-

pH 8.0, 37°C

0.45

1-thiophen-2-ylmethanamine

-

pH 8.0, 37°C

0.11

1-thiophen-3-ylmethanamine

-

pH 8.0, 37°C

0.0012

2-bromo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.00073 - 0.021

2-bromo-6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

0.025

2-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.0026

2-nitro-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.22

2-Phenylethylamine

-

pH 8.0, 37°C

0.3

2-thiophen-2-ylethanamine

-

pH 8.0, 37°C

0.00082

3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00015

3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.0000018 - 0.000315

3-(fluoromethyl)-7-(thiomorpholin-4-ylsulfonyl)-1,2,3,4-tetrahydroisoquinoline

0.00015

3-(fluoromethyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00013

3-(fluoromethyl)-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.000017 - 0.000035

3-(fluoromethyl)-N-(3,3,3-trifluoropropyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

0.017

3-(trifluoromethyl)-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.0066

3-butyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.0034

3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0032

3-difluoromethyl-7-(ethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.00025

3-difluoromethyl-7-(N-2,2,2-trifluoroethylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0053

3-difluoromethyl-7-(N-3-methoxypropylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.037

3-difluoromethyl-7-(N-4-nitrophenylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0021

3-difluoromethyl-7-(propylaminosulfonyl)-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.000094

3-difluoromethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0031

3-difluoromethyl-7-cyano-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0002

3-difluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.006

3-difluoromethyl-7-methylsulfonyl-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.00017

3-difluoromethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.000067

3-difluoromethyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0018

3-ethyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.00049

3-ethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00051

3-ethyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.000073

3-fluoromethyl-7-iodo-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

0.00035

3-hydroxyethyl-7-bromo-1,2,3,4-tetrahydroisoquinoline

-

0.00051

3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

0.000047

3-hydroxymethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

0.0017

3-hydroxypropyl-7-bromo-1,2,3,4-tetrahydroisoquinoline

-

0.0014

3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

0.0046

3-isopropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.0014

3-methyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.000077

3-methyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.000067

3-methyl-1,2,3,4-tetrahydro[1]benzothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.000072

3-methyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.000034

3-methyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.00012

3-propyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.00092

3-propyl-N-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

-

pH 8.0, 37°C

0.037

4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.015

4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile

-

pH 8.0, 37°C

0.1

4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxamide

-

pH 8.0, 37°C

0.04

6-(trifluoromethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.0058

6-methyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

-

pH 8.0, 37°C

0.0000031

7,8-dichloro-1,2,3,4-tetrahydroisoquinoline

0.0009

7-(N-4-chlorophenylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.0056

7-(N-butylaminosulfonyl)-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.033

7-aminosulfonyl-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

0.00068

7-aminosulfonyl-3-difluoromethyl-1,2,3,4-tetrahydroisoquinoline

-

radiochemical assay, inhibition constants are determined using four concentrations of phenylethanolamine as the variable substrate, and three concentrations of inhibitor

0.00022

7-bromo-1,2,3,4-tetrahydrobenzo[h]isoquinoline

-

0.00022

7-bromo-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

pH 8.0, 37°C

0.000056

7-bromo-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.000023

7-bromo-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.0076

7-bromo-3-butyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00048

7-bromo-3-ethyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00035

7-bromo-3-hydroxyethyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

0.000012

7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

0.0017

7-bromo-3-hydroxypropyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

0.0044

7-bromo-3-isopropyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.000017

7-bromo-3-methyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.011

7-bromo-3-pentyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00048

7-bromo-3-propyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.0023

7-cyano-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

0.00091

7-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

0.00004 - 0.00074

7-iodo-1,2,3,4-tetrahydroisoquinoline

0.0021

7-methoxy-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

0.0009

7-nitro-1,2,3,4-tetrahydrobenz[h]isoquinoline

-

0.00007 - 0.00137

7-nitro-1,2,3,4-tetrahydroisoquinoline

0.0098

7-nitro-3-pentyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00053

7-nitro-3-propyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0, 37°C

0.00028

7-sulfonamido-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

0.000012

8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine

-

pH 8.0

0.17

benzylamine

-

pH 8.0, 37°C

0.0000013 - 0.00021

N-(4-chlorophenyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

0.000001 - 0.00027

N-(4-chlorophenyl)-3-(fluoromethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

0.0000014 - 0.000039

N-(4-chlorophenyl)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

0.0000049

R-(+)-7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline

-

pH 8.0

additional information

-

enzyme kinetics using competitive tight-binding inhibition routine

-

0.0019

LY134046

Homo sapiens

-

selective inhibitor, IC50: 0.0019 mM

0.0000137

-

pH 8.5, 37°C

718693

8

8.5

-

assay at

718693

30

-

assay at

37

-

-

-

pheochromocytoma cell

-

neuroendocrine tumour of chromaffin cells

672987

additional information

-

tissue from pheochromocytoma tumor specimens

P11086 pBLAST

PNMT_HUMAN

282

0

30855

Swiss-Prot

Show Sequence

other Location (Reliability: 3)

42 entries

30000

-

SDS-PAGE

30280

-

analytical ultracentrifugation, non tagged phenylethanolamine N-methyltransferase, monomer

60550

-

analytical ultracentrifugation, non tagged phenylethanolamine N-methyltransferase, dimer

dimer

-

gel filtration reveals the presence of two species at elution volumes consistent with monomeric and dimeric human phenylethanolamine N-methyltransferase. The more prominent peak corresponds to the dimer form. The amount of dimer can be reduced either by using a more elute concentration of the protein or by the addition of 0.5 mM DTT to the running buffer. SDS-PAGE can not distinguish between the two forms. Native PAGE clearly distinguishes between the two forms of human phenylethanolamine N-methyltransferase. Crystals from the dimer fraction grow faster. Monomer and dimer human phenylethanolamine N-methyltransferase have similar kinetic constatns. The monomer-dimer equilibruim in analytical ultracentrifugation for the dimer frations of phenylethanolamine N-methyltransferase-His and C48A phenylethanolamine N-methyltransferase is 10fold lower than for the monomer fractions (Kd 35-64 microM and 305-551 microM, respectively).

-

hanging drop vapor diffusion using drops of 1 microl of protein and 1 microl of precipitant over 100 microl of precipitant [ 5-8% PEG 6K, 0.25 M LiCl, and 0.1 M sodium cacodylate (pH 5.5-6.0)]

hanging drop vapour diffusion on 3 M tape with 1 microl protein/ligand mixture plus 1 microl precipitant over 100 microl precipitant (0.6-0.8 M NH4H2PO4, 0.1 M citrate pH 5.3-5.8). The human phenylethanolamine N-methyltransferase S-adenosyl-L-homocysteine SKF 64139 structure is solved by difference Fourier methods and refines at 2.4 A resolution. A hydrophilic inhibitor does not bind in a distinclty differnt orientation than a hydrophobic inhibitor.

in complex with S-adenosyl-L-homocysteien and either 7-iodo-1,2,3,4-tetrahydroisoquinoline or 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine or 7-sulfonamido-1,2,3,4-tetrahydroisoquinoline

crystallized in complex with an inhibitor and the cofactor product S-adenosyl-L-homocysteine using hanging-drop technique with PEG 6000 and lithium chloride as precipitant

-

639449

hanging drop vapour diffusion method is used with 2 mircol drops on 3 M sealed over 500 mircol or 100 microl precipitant in 24-well or 96-well trays. In the absence of reducing agents crystals grow on protein concentrations of 30 to 40 mg/ml and appear in two or three days. The addition of DTT inhibits formation of crystals under the same condition. Reduced and oxidized glutathione are added to PEG/LiCl crystallisation conditions, crystals only grow in drops where the amount of oxidized glutathione is higher than reduced, the ratio of 1:20 (reduced glutathione/oxidized glutathione) gives the largest crystals.

-

in complex with inhibitors 3-hydroxymethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline, 7-bromo-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline, 3-hydroxyethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline, 3-hydroxypropyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

-

model is prepared on the basis of X-ray crystal structure of hPNMT in complex with S-adenosyl-L-homocysteine (AdoHcy) and the inhibitor SK&F 29661

-

purified recombinant His6-tagged wild-type and mutant K75A enzymes in complex with S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, and with inhibitors (R)-4, (R)-5, (R)-6, and (R)-7, X-ray diffraction structure determination and analysis at 2.0-2.8 A resolution

-

D267A

higher Km and lower kcat values than wild type enzyme

E185A

Kcat value is reduced by 15fold. Similar Km for phenylethanolamine and slightly lower Km for AdoMet than the wild type enzyme.

E185D

Kcat value is reduced by 3fold. Moderately increased Km values for phenylethanolamine and AdoMet

E185Q

kcat value reduced by about 300fold. Similar Km for phenylethanolamine and slightly lower Km for AdoMet than the wild type enzyme.

E219A

higher Km and lower kcat values than wild type enzyme

E219Q

The E219Q mutant has no effect on the catatlytic rate.

K57A

higher Km and higher kcat values than wild type enzyme

V53A

higher Km and higher kcat values than wild type enzyme

Y35F

reduced level of binding of phenylethanolamine and AdoMet. The catalytic rate is not greatly affected by the Y35F mutation.

C131S

-

mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme

C139A

-

the C139A mutant separates into two forms on gel filtration, consistent with a monomer and dimer form, the equilibrium is significantly shifted in favour of the monomer. C139A mutant has similar kinetic constants as the wild type human phenylethanolamine N-methyltransferase

C139S

-

mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme

C183S

-

mutant enzyme shows markedly reduced enzyme activity with less than 3% of the maximal activity of the wild-type enzyme, and ca. sixfold increased apparent KM-value for both substrates

C48A

-

the C48A mutant separates into two forms on gel filtration, consistent with a monomer and dimer form, the equilibrium is significantly shifted in favour of the monomer. C48A mutant has similar kinetic constants as the wild type human phenylethanolamine N-methyltransferase. The monomer-dimer equilibrium in analytical ultracentrifugation for the dimer fractions of phenylethanolamine N-methyltransferase-His and C48A phenylethanolamine N-methyltransferase is 10fold lower than for the monomer fractions (Kd 35-64 microM and 305-551 microM, respectively). The relative Kd values show that C48A phenylethanolamine N-methyltransferase is less likely to form dimer than phenylethanolamine N-methyltransferase-His.

C48A/C139A

-

similar kinetic constants as the wild type human phenylethanolamine N-methyltransferase

C48S

-

mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme

C60S

-

mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme

C91S

-

mutant enzyme shows similar KM-values and maximal velocity to those of the wild-type enzyme

E185Q

-

mutant has the same Km value as the wild-type hPNMT but extremely lower kcat value. E185Q mutation presents obvious structural changes in the active site

E219Q

-

mutation has little effect on the kcat value. The bridge water still forms two hydrogen bonds between Gln219 and Glu185

K75A

-

crystal structure determination and comparison to the wild-type enzyme structure

additional information

-

rs3764351 and rs876493 polymorphisms in gene PNMT are correlated to reward dependence, overview

-

His-Select HC nickel affninity column and gel filtration

6X-histidine tagged phenylethanolamine N-methyltransferase purified on a 10 ml column and with gel filtration. Non-tagged phenylethanolamine N-methyltransferase is purified with DEAE-Sepharose and gel filtration.

-

recombinant C-terminally His6-tagged wild-type and mutant enzymes

-

using Ni-NTA chromatography

-

718693, 720467

expressed in Escherichia coli

expressed in Escherichia coli strain BL21(DE3)-pLysS

C-terminally His-tagged hPNMT is expressed in Escherichia coli

-

expressed in Escherichia coli

-

expressed in Escherichia coli as a His-tagged fusion protein

-

718693, 720467

expressed in Escherichia coli strain BL21(DE3)pLysS

-

expressed in Eschrischia coli

-

expression of C-terminally His6-tagged wild-type and mutant enzymes

-

expression of C-terminally His6-tagged wild-type enzyme

-

expression of wild-type enzyme and mutant enzymes in Escherichia coli

-

gene PNMT, genotyping of rs3764351 and rs876493 polymorphisms haplotypes in Japanese women, overview

-

human phenylethynolamine N-methyltransferase with a C-terminal hexahistidine tag is expressed in Escherichia coli

-

strong relationship between PNMT gene expression and tissue epinephrine levels in human pheochromocytomas

-

analysis

-

method to measure tissue contents and activity of phenylethanolamine N-methyltransferase, utilizing double stable isotope ultra performance liquid chromatography-tandem mass spectrometry. The method is based on measurement of deuterium-labeled epinephrine produced from reaction of norepinephrine with deuterium-labeled S-adenosyl-Lmethionine as the methyl donor. In addition to enzyme activity the method allows for determination of tissue contents of PNMT using human recombinant enzyme for calibration. The calibration curve for epinephrine is linear over the range of 0.1 to 5000 pM, with 0.5 pM epinephrine representing the lower limit of quantification

medicine

-

strong relationship between PNMT gene expression and tissue epinephrine levels in human pheochromocytomas

additional information

4 entries

639449

Begun, J.; McLeish, M.J.; Caine, J.M.; Palant, E.; Grunewald, G.L.; Martin, J.L.

Crystallization of PNMT, the adrenaline-synthesizing enzyme, is critically dependent on a high protein concentration

Acta Crystallogr. Sect. D

58

314-315

2002

Homo sapiens

11807261

Kaneda, N.; Hikita, K.; Naruse, Y.; Fukuo, T.; Matsubara, K.; Nagatsu, T.

Identification of the essential cysteinyl residue located in the active site of human phenylethanolamine N-methyltransferase

Biochem. Biophys. Res. Commun.

249

405-409

1998

Homo sapiens

9712709

Gearhart, D.A.; Neafsey, E.J.; Collins, M.A.

Phenylethanolamine N-methyltransferase has beta-carboline 2N-methyltransferase activity: hypothetical relevance to Parkinson's disease

Neurochem. Int.

40

611-620

2002

Homo sapiens

11900856

Grunewald, G.L.; Romero, F.A.; Chieu, A.D.; Fincham, K.J.; Bhat, S.R.; Criscione, K.R.

Exploring the active site of phenylethanolamine N-methyltransferase: 3-alkyl-7-substituted-1,2,3,4-tetrahydroisoquinoline inhibitors

Bioorg. Med. Chem.

13

1261-1273

2005

Homo sapiens

15670935

Wu, Q.; Criscione, K.R.; Grunewald, G.L.; McLeish, M.J.

Phenylethanolamine N-methyltransferase inhibition: re-evaluation of kinetic data

Bioorg. Med. Chem. Lett.

14

4217-4220

2004

Homo sapiens

15261273

McMillan, F.M.; Archbold, J.; McLeish, M.J.; Caine, J.M.; Criscione, K.R.; Grunewald, G.L.; Martin, J.L.

Molecular recognition of sub-micromolar inhibitors by the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase

J. Med. Chem.

47

37-44

2004

Homo sapiens (P11086), Homo sapiens

14695818

Gee, C.L.; Tyndall, J.D.; Grunewald, G.L.; Wu, Q.; McLeish, M.J.; Martin, J.L.

Mode of binding of methyl acceptor substrates to the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase: implications for catalysis

Biochemistry

44

16875-16885

2005

Homo sapiens (P11086), Homo sapiens

16363801

Gee, C.L.; Nourse, A.; Hsin, A.Y.; Wu, Q.; Tyndall, J.D.; Grunewald, G.L.; McLeish, M.J.; Martin, J.L.

Disulfide-linked dimers of human adrenaline synthesizing enzyme PNMT are catalytically active

Biochim. Biophys. Acta

1750

82-92

2005

Homo sapiens

15893506

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

Bioorg. Med. Chem.

15

1298-1310

2007

Homo sapiens, Rattus norvegicus

17126018

Grunewald, G.L.; Romero, F.A.; Seim, M.R.; Criscione, K.R.; Deupree, J.D.; Spackman, C.C.; Bylund, D.B.

Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines

Bioorg. Med. Chem. Lett.

15

1143-1147

2005

Homo sapiens

15686930

672582

Grunewald, G.L.; Lu, J.; Criscione, K.R.; Okoro, C.O.

Inhibitors of phenylethanolamine N-methyltransferase devoid of alpha2-adrenoceptor affinity

Bioorg. Med. Chem. Lett.

15

5319-5323

2005

Homo sapiens

16169723

672987

Cleary, S.; Brouwers, F.M.; Eisenhofer, G.; Pacak, K.; Christie, D.L.; Lipski, J.; McNeil, A.R.; Phillips, J.K.

Expression of the noradrenaline transporter and phenylethanolamine N-methyltransferase in normal human adrenal gland and phaeochromocytoma

Cell Tissue Res.

322

443-453

2005

Homo sapiens, Rattus norvegicus

16047163

Wu, Q.; Gee, C.L.; Lin, F.; Tyndall, J.D.; Martin, J.L.; Grunewald, G.L.; McLeish, M.J.

Structural, mutagenic, and kinetic analysis of the binding of substrates and inhibitors of human phenylethanolamine N-methyltransferase

J. Med. Chem.

48

7243-7252

2005

Homo sapiens (P11086), Homo sapiens

16279783

Grunewald, G.L.; Seim, M.R.; Lu, J.; Makboul, M.; Criscione, K.R.

Application of the Goldilocks effect to the design of potent and selective inhibitors of phenylethanolamine N-methyltransferase: balancing pKa and steric effects in the optimization of 3-methyl-1,2,3,4-tetrahydroisoquinoline inhibitors by beta-fluorinatio

J. Med. Chem.

49

2939-2952

2006

Homo sapiens

16686536

Grunewald, G.L.; Seim, M.R.; Regier, R.C.; Martin, J.L.; Gee, C.L.; Drinkwater, N.; Criscione, K.R.

Comparison of the binding of 3-fluoromethyl-7-sulfonyl-1,2,3,4-tetrahydroisoquinolines with their isosteric sulfonamides to the active site of phenylethanolamine N-methyltransferase

J. Med. Chem.

49

5424-5433

2006

Homo sapiens (P11086), Homo sapiens

16942016

677224

Goncalvesova, E.; Krizanova, O.; Micutkova, L.; Mravec, B.; Ksinantova, L.; Fabian, J.; Kvetnansky, R.

Phenylethanolamine N-methyltransferase gene expression in transplanted human heart

Transplant. Proc.

37

1340-1342

2005

Homo sapiens

15848714

Grunewald, G.L.; Seim, M.R.; Bhat, S.R.; Wilson, M.E.; Criscione, K.R.

Synthesis of 4,5,6,7-tetrahydrothieno[3,2-c]pyridines and comparison with their isosteric 1,2,3,4-tetrahydroisoquinolines as inhibitors of phenylethanolamine N-methyltransferase

Bioorg. Med. Chem.

16

542-559

2008

Homo sapiens

18024134

Yamano, E.; Isowa, T.; Nakano, Y.; Matsuda, F.; Hashimoto-Tamaoki, T.; Ohira, H.; Kosugi, S.

Association study between reward dependence temperament and a polymorphism in the phenylethanolamine N-methyltransferase gene in a Japanese female population

Compr. Psychiatry

49

503-507

2008

Homo sapiens

18702937

Gee, C.L.; Drinkwater, N.; Tyndall, J.D.; Grunewald, G.L.; Wu, Q.; McLeish, M.J.; Martin, J.L.

Enzyme adaptation to inhibitor binding: A cryptic binding site in phenylethanolamine N-methyltransferase

J. Med. Chem.

50

6441

2007

Homo sapiens

-

718693

Grobe, N.; Ren, X.; Kutchan, T.M.; Zenk, M.H.

An (R)-specific N-methyltransferase involved in human morphine biosynthesis

Arch. Biochem. Biophys.

506

42-47

2011

Homo sapiens

21093406

Drinkwater, N.; Vu, H.; Lovell, K.M.; Criscione, K.R.; Collins, B.M.; Prisinzano, T.E.; Poulsen, S.A.; McLeish, M.J.; Grunewald, G.L.; Martin, J.L.

Fragment-based screening by X-ray crystallography, MS and isothermal titration calorimetry to identify PNMT (phenylethanolamine N-methyltransferase) inhibitors

Biochem. J.

431

51-61

2010

Homo sapiens

20642456

Hou, Q.Q.; Wang, J.H.; Gao, J.; Liu, Y.J.; Liu, C.B.

QM/MM studies on the catalytic mechanism of phenylethanolamine N-methyltransferase

Biochim. Biophys. Acta

1824

533-541

2012

Homo sapiens

22326747

Kang, D.I.; Lee, J.Y.; Kim, W.; Jeong, K.W.; Shin, S.; Yang, J.; Park, E.; Chae, Y.K.; Kim, Y.

Discovery of novel human phenylethanolamine N-methyltransferase (hPNMT) inhibitors using 3D pharmacophore-based in silico, biophysical screening and enzymatic activity assays

Mol. Cells

29

595-602

2010

Homo sapiens

20496117

Qin, N.; Peitzsch, M.; Menschikowski, M.; Siegert, G.; Pacak, K.; Eisenhofer, G.

Double stable isotope ultra performance liquid chromatographic-tandem mass spectrometric quantification of tissue content and activity of phenylethanolamine N-methyltransferase, the crucial enzyme responsible for synthesis of epinephrine

Anal. Bioanal. Chem.

405

1713-1719

2013

Homo sapiens

23224622