Information on EC 2.1.1.8 - histamine N-methyltransferase

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
2.1.1.8
-
RECOMMENDED NAME
GeneOntology No.
histamine N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
ordered sequential bi bi reaction mechanism with S-adenosylmethionine as the first substrate and histamine as the second substrate, 1-methylhistamine is the first product to leave and S-adenosylhomocysteine the second; sequential reaction mechanism
-
S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
ordered steady state mechanism with S-adenosylmethionine being the first substrate to bind to the enzyme and N-methylhistamine being the first product to dissociate
-
S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
2 half-reactions in a ping pong mechanism with the intermediate formation of a methylated enzyme
-
S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
N-methylation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
histamine degradation
-
Histidine metabolism
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:histamine N-tele-methyltransferase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
histamine 1-methyltransferase
-
-
-
-
histamine methyltransferase
-
-
-
-
histamine methyltransferase
-
-
histamine N-methyltransferase
-
-
histamine N-methyltransferase
-
-
histamine N-methyltransferase
-
-
histamine N-methyltransferase
-
-
histamine-methylating enzyme
-
-
-
-
histamine-N-methyltransferase
-
-
HMT
-
-
HNMT
-
-
HNMT
-
-
imidazole methyltransferase
-
-
-
-
imidazole N-methyltransferase
-
-
-
-
imidazolemethyltransferase
-
-
-
-
methyltransferase, histamine
-
-
-
-
Ntau-methyltransferase
-
-
S-adenosylmethionine-histamine N-methyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9029-80-5
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + (+/-)beta-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + (R)-alpha-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + (R)-alpha-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + (S)-alpha-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + (S)-alpha-methylhistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
P50135
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
highly specific for histamine
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
highly specific for histamine
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
highly specific for histamine
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
highly specific for histamine
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
-
given a negative correlation between diamine oxidase and HMT activities, the fraction of catabolized histamine decreases with increasing HMT activity
-
-
?
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + N-methylhistamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + homohistamine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
possible role in modulation of histamine mediated reactions in skin
-
-
-
additional information
?
-
-
major enzyme for histamine inactivation in mammalian tissues
-
-
-
additional information
?
-
-
major enzyme for histamine inactivation in mammalian tissues
-
-
-
additional information
?
-
-
major pathway of histamine metabolism in mammals
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
possible role in modulation of histamine mediated reactions in skin
-
-
-
additional information
?
-
-
major enzyme for histamine inactivation in mammalian tissues
-
-
-
additional information
?
-
-
major enzyme for histamine inactivation in mammalian tissues
-
-
-
additional information
?
-
-
major pathway of histamine metabolism in mammals
-
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(5'-amino-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[4-(3-piperidin-1-yl-propoxy)-phenyl]-methanone
-
50% inhibition at 0.0020 mM, simultaneously a highly potent H3 receptor ligand
(5'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-[4-(3-piperidin-1-yl-propoxy)-phenyl]-methanone
-
50% inhibition at 0.0015 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-[4-(3-piperidin-1-yl-propoxy)-benzyl]-amine
-
50% inhibition at 0.0042 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-{2-[4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl}-amine
-
50% inhibition at 0.0028 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-{3-[4-(3-piperidin-1-yl-propoxy)-phenyl]-propyl}-amine
-
50% inhibition at 0.0017 mM, simultaneously a highly potent H3 receptor ligand
(5-nitro-pyridin-2-yl)-{4-[4-(3-piperidin-1-yl-propoxy)-phenyl]-butyl}-amine
-
50% inhibition at 0.0017 mM, simultaneously a highly potent H3 receptor ligand
(R)-chloroquine
-
50% inhibition at 0.018 mM, liver enzyme, 50% inhibition at 0.0022 mM, brain enzyme
(S)-chloroquine
-
50% inhibition at 0.005 mM, liver enzyme, 50% inhibition at 0.007 mM, brain enzyme
1-(3-(4-(3,4-dihydro-2H-pyrrol-5-yl)phenoxy)propyl)piperidine
-
50% inhibition at 0.0090 mM, simultaneously a highly potent H3 receptor ligand
1-Methylhistamine
-
strong
1-Methylhistamine
-
-
2-(3-piperidin-1-ylpropoxy)-1,3-benzothiazole quinoline
-
50% inhibition at 0.021 mM, simultaneously a highly potent H3 receptor ligand
-
2-(4-hydroperoxyphenyl)-6-methyl-4H-chromen-4-one
-
-
2-Bromolysergic acid diethylamide
-
-
2-Methylhistamine
-
strong
3,6-dimethyl-2-phenyl-4H-chromen-4-one
-
-
3-bromo-6-chloro-2-phenyl-4H-chromen-4-one
-
-
3-bromo-6-methyl-2-phenyl-4H-chromen-4-one
-
-
3-chloro-6-methyl-2-phenyl-4H-chromen-4-one
-
-
3-Methylhistamine
-
strong
4-(dimethylamino)butyl carbamimidothioate
-
SKF-91488
5-Methylhistamine
-
weak
5-nitro-2-(3-piperidin-1-ylpropoxy)pyridine
-
50% inhibition at 0.034 mM, simultaneously a highly potent H3 receptor ligand
5-nitro-N-(4-(3-piperidin-1-ylpropoxy)phenyl)pyridin-2-amine
-
50% inhibition at 0.0038 mM, simultaneously a highly potent H3 receptor ligand
6-(3-piperidin-1-ylpropoxy)pyridin-3-amine
-
50% inhibition at 0.053 mM, simultaneously a potent H3 receptor ligand
6-chloro-2-phenyl-4H-chromen-4-one
-
-
6-methyl-2-phenyl-4H-chromen-4-one
-
-
6-piperidin-1-yl-1-[4-(3-piperidin-1-yl-propoxy)-phenyl]-hexan-1-one
-
50% inhibition at 0.0089 mM, simultaneously a highly potent H3 receptor ligand
7-chloro-4-(3-piperidin-1-ylpropoxy)quinoline
-
50% inhibition at 0.0026 mM, simultaneously a potent H3 receptor ligand
8-(3-(1H-imidazol-4-yl)propoxy)-5-nitroquinoline
-
50% inhibition at 0.0117 mM, simultaneously a highly potent H3 receptor ligand
8-bromo-6-chloro-2-phenyl-4H-chromen-4-one
-
-
8-bromo-6-methyl-2-phenyl-4H-chromen-4-one
-
-
amodiaquine
-
-
amodiaquine
-
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
Biogenic amines
-
-
-
bromo-lysergic acid diethylamide
-
55% inhibition at 0.005 mM
Chlorpromazine
-
60% inhibition at o.oo5 mM
d-Chlorpheniramine
-
-
diphenhydramine
-
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
histamine
-
0.025-0.1 mM
histamine
-
not
Impromidine
-
competitive, reversible
iodoacetamide
-
complete inhibition at 0.01 mM
iodoacetamide
-
activation
Methylhistamine
-
40% inhibition at 0.1 mM
Methylhistamine
-
-
Methylhistamine
-
-
methylthioadenosine
-
-
Metoprine
-
-
N-(2-(1H-imidazol-4-yl)ethyl)-1,2,3,4-tetrahydroacridin-9-amine
-
50% inhibition at 0.000086 mM, simultaneously a highly potent H3 receptor ligand
N-(2-(1H-imidazol-4-yl)ethyl)-N-methylquinolin-4-amine
-
50% inhibition at 0.000079 mM, simultaneously a highly potent H3 receptor ligand
N-(2-(1H-imidazol-4-yl)ethyl)quinolin-4-amine
-
50% inhibition at 0.000055 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)-1,2,3,4-tetrahydroacridin-9-amine
-
50% inhibition at 0.000035 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)-2-methylquinolin-4-amine
-
50% inhibition at 0.000054 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)-N-methylquinolin-4-amine
-
50% inhibition at 0.000035 mM, simultaneously a highly potent H3 receptor ligand
N-(3-(1H-imidazol-4-yl)propyl)quinolin-4-amine
-
50% inhibition at 0.000024 mM, simultaneously a highly potent H3 receptor ligand
N-ethylmaleimide
-
-
N-[2(benzhydryloxy)ethyl] N N-dimethylamine
-
diphenhydramine, competitive inhibitor
N2-[2-[4-(3-piperidin-1-yl-propoxy)-phenyl]-ethyl]-pyridine-2,5-diamine
-
50% inhibition at 0.00031 mM, simultaneously a highly potent H3 receptor ligand
N2-[3-[4-(3-piperidin-1-yl-propoxy)-phenyl]-propyl]-pyridine-2,5-diamine
-
50% inhibition at 0.0013 mM, simultaneously a highly potent H3 receptor ligand
N2-[4-[4-(3-piperidin-1-yl-propoxy)-phenyl]-butyl]-pyridine-2,5-diamine
-
50% inhibition at 0.00034 mM, simultaneously a highly potent H3 receptor ligand
Nalpha-methylhistamine
-
weak
p-chloromercuribenzoate
-
90% inhibition at 0.01 mM
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
complete inhibition at 0.1 mM
S-adenosylhomocysteine
-
-
S-adenosylhomocysteine
-
-
S-adenosylhomocysteine
-
-
serotonin
-
33% inhibition at 0.005 mM
SKF 91488
-
-
tacrine
-
50% inhibition at 0.00046 mM for enzyme of embryonic kidney, at 0.0007 mM for recombinant brain enzyme
tacrine
-
50% inhibition at 0.00029 mM
tacrine
-
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
tryptamine
-
and the hydroxyl derivative
tyramine
-
and the hydroxyl derivative
[4-(3-piperidin-1-yl-propoxy)-phenyl]-(1-quinolin-4-yl-piperidin-4-yl)-methanone
-
50% inhibition at 0.00031 mM, simultaneously a highly potent H3 receptor ligand
Metoprine
-
potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
additional information
-
not inhibitory: S-adenosyl-L-methionine
-
additional information
-
overview: adenosine analogs bearing a lipophilic side chain
-
additional information
-
not inhibitory: galanthamine up to 0.001 mM
-
additional information
-
near the N-terminus of HNMT, several aromatic residues (Phe9, Tyr15, and Phe19) adopt different rotamer conformations or become disordered in the enzyme-inhibitor complexes, accommodating the diverse, rigid hydrophobic groups of the inhibitors, maximized shape complementarity between the protein aromatic side-chains and aromatic rings of the inhibitors are responsible for the tight binding of the different inhibitors
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5-Methylhistamine
-
0.001-0.5 mM, activation
alpha,Nalpha-Dimethylhistamine
-
activation
iodoacetamide
-
inhibition
iodoacetamide
-
activation
iodoacetic acid
-
activation
N',N'-dimethylhistamine
-
0.001-0.5 mM, activation
Nalpha-methylhistamine
-
0.001-0.5 mM, activation
Succinic anhydride
-
activation
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0042
-
histamine
-
-
0.0061
-
histamine
-
-
0.012
-
histamine
-
-
0.014
-
histamine
-
-
0.026
-
histamine
-
-
0.035
-
histamine
-
-
0.0017
-
S-adenosyl-L-methionine
-
-
0.0018
-
S-adenosyl-L-methionine
-
-
0.006
-
S-adenosyl-L-methionine
-
-
0.0071
-
S-adenosyl-L-methionine
-
-
0.04
-
S-adenosyl-L-methionine
-
-
0.38
-
S-adenosyl-L-methionine
-
-
0.043
-
histamine
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00005
-
Amodiaquin
-
-
0.0000186
-
amodiaquine
-
-
0.0007
-
d-Chlorpheniramine
-
-
0.008
-
Dimaprit
-
-
0.000091
-
Metoprine
-
-
0.001
-
SKF 91488
-
-
0.0000382
-
tacrine
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000022
-
-
large intestine, saline treated
0.000028
-
-
large intestine, amitriptyline treated
0.000036
-
-
kidney, saline treated
0.000038
-
-
lung, saline treated
0.000052
-
-
lung, amitriptyline treated
0.000054
-
-
kidney, amitriptyline treated
0.00008
-
-
cerebrum, saline treated
0.000101
-
-
small intestine, saline treated
0.000121
-
-
cerebrum, amitriptyline treated
0.000132
-
-
spleen, saline treated
0.000163
-
-
small intestine, amitriptyline treated
0.000165
-
-
spleen, amitriptyline treated
0.517
-
-
-
4.47
-
-
37°C
10.4
-
-
-
25.4
-
-
-
additional information
-
-
-
additional information
-
-
HPLC assay method
additional information
-
-
enzyme activities are increased in tissues of amitriptyline treated guinea pigs
additional information
-
-
enzyme activities are increased in spleen and kidney of amitriptyline treated rats
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.2
7.4
-
-
7.2
7.4
-
-
7.5
-
-
2 optima at pH 7.5 and pH 9.0, brain enzyme
8.3
-
-
N-methylhistamine
8.5
9
-
kidney enzyme
9
-
-
2 optima: pH 7.5 and pH 9.0, brain enzyme
9
-
-
kidney
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
10.5
-
about 50% of maximum activity at pH 6.5 and pH 10.5, N-methylhistamine
7.3
10.3
-
about 50% of maximum activity at pH 7.3 and pH 10.3
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
recombinant enzyme from brain
Manually annotated by BRENDA team
-
HMT activity comparable to activity in the jejunum
Manually annotated by BRENDA team
-
columnar epithelium
Manually annotated by BRENDA team
-
HMT activity comparable to activity in the colon
Manually annotated by BRENDA team
-
embryonic cells
Manually annotated by BRENDA team
-
RNA expression is amplified after treatment with amitriptyline
Manually annotated by BRENDA team
-
antrum mucosa
Manually annotated by BRENDA team
-
fundic mucosa
Manually annotated by BRENDA team
-
RNA expression is amplified after treatment with amitriptyline
Manually annotated by BRENDA team
additional information
-
tissue distribution
Manually annotated by BRENDA team
additional information
-
inhibitory activity of adenosine analogs
Manually annotated by BRENDA team
additional information
-
tissue distribution
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
29000
-
-
gel filtration, SDS-PAGE
31500
-
-
SDS-PAGE, gel filtration
34800
-
-
gel filtration
36000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 33400, SDS-PAGE
?
-
x * 35000, SDS-PAGE
?
-
x * 33200, SDS-PAGE
?
-
x * 33000, SDS-PAGE
?
-
x * 32000, SDS-PAGE
?
-
x * 33000, deduced from DNA sequence
?
-
x * 32000, SDS-PAGE
monomer
-
1 * 29000, SDS-PAGE
monomer
-
1 * 31500, SDS-PAGE
additional information
-
two polymorphic forms, Thr105 corresponds to high activity, Ile105 corresponds to low activity phenotype
additional information
-
theoretical 3D model of isoforms, Ile105 energetically destabilizes
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
by hanging-drop method, HNMT bound to four different inhibitors at resolution limits of 1.9 A (diphenhydramine), 2.3 A (amodiaquine), 2.48 A (metoprine), and 2.97 A (tacrine) and in complex with S-adenosyl-L-homocysteine
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
90 min, 1 mM dithiothreitol, stable, 40% loss of activity without addition of dithiothreitol
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dithiothreitol, 1 mM, stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80°C, 3 months
-
-80°C, 10 mM potassium phosphate buffer, pH 7.4, 10% glycerol, 1 mM dithiothreitol, 8 months, 16% loss of activity
-
-80°C, 3 months
-
-80°C, 5 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant protein
-
simultaneous purification of enzyme and diamine oxidase
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
by molecular cloning
-
expressed in HMC-1 cells
-
kidney, intestine
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
HMT expression is elevated in reg6 mutants
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
T105I
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functional polymorphism, about 50% reduction of enzyme activity
T105I
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common threonine-isoleucine polymorphism at residue 105, showing decreased activity and lower protein levels than the 105T protein. Molecular dynamic simulations at 37°C indicate that replacing Thr with the larger Ile residue leads to greater burial of residue 105 and heightened intramolecular interactions between residue 105 and residues within helix R3 and strand a3. This altered, tighter packing is translated to the active site, resulting in the reorientation of several cosubstrate-binding residues
T105I
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Thr105Ile polymorphism is analyzed whether it is associated with alcoholism in German Caucasians. No significant difference is found in the frequency of the Ile105 allele between alcoholics and controls. Likewise, genotype distributions does not differ significantly. Frequency of the Ile105 allele is significantly lower in male alcoholics with a family history of alcoholism compared to that in male alcoholics without a family history of alcoholism
T105I
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Thr105Ile polymorphism of the HNMT enzyme is analyzed in patients with essential tremor. Leukocytary DNA from 204 essential tremor patients and a control group of 295 unrelated healthy individuals is studied for the nonsynonymous HNMT Thr105Ile polymorphism by using amplification-restriction analyses. Patients with essential tremor show a higher frequency of homozygous HNMT 105Thr genotypes leading to high metabolic activity with a statistically significant gene-dose effect, as compared to healthy subjects
T105I
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an association of the HNMT Thr105Ile polymorphism with Parkinson’s disease is observed
C314T
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PCR reaction-restriction fragment length polymorphism assay is used to identify the polymorphism of the point mutation C314T of HNMT gene of 498 Chinese patients with duodenal ulcer and 151 healthy individuals. In normal controls, the allele frequency of HNMT T314 is 3.3%, which is significantly lower than American Caucasians. The HNMT T314 allele is detected in 3.5% of the duodenal ulcer patients. In cases and controls, the frequency of C/C genotypes are 93.0% and 93.4%, respectively. The HNMT T/T genotype is not found in this population. No significant differences is seen in both genotype frequencies and allele frequencies between duodenal ulcer groups and controls
additional information
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the A939G polymorphism is significantly associated with the aspirin intolerant chronic urticaria phenotype, while no association is found with the C314T polymorphism, the 939A allele gives lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele, patients with the 939A allele have lower HNMT activity in red blood cell lysates and higher histamine release from their basophils
T105I
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naturally occuring mutation, association found with Parkinson's disease
additional information
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subcutaneous injection of amodiaquine in mice with propionibacterium acnes-primed and lipopolysaccharide (LPS)-induced hepatitis significantly increases the histamine levels in the liver in comparison to saline treated mice. Pretreatment with amodiaquine also improves the survival rate of the hepatitis mice, and this improvement is partially associated with the decrease in serum levels of aspartate aminotransferase and alanine aminotransferase. Amodiaquine partially suppresses increases of tumor necrosis factor (TNF)-alpha in the serum and TNF-alpha mRNA expression in the liver
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
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guinea-pig HNMT has 292 amino acid residues, its sequences are more similar to the human and pig sequences than to the mouse and rat sequences, respectively
medicine
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T105I mutation is more abundant among alcoholics from Finnish Caucasion and Plains Indian American populations. Decreased histamine level in central nervous system may be a risk factor in alcoholism and associated with higher levels of trait anxiety
medicine
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in patients with food allergy, median enzyme activity, as well as median diamone oxidase activity, are significantly decreased compared to controls. Histamine content is elevated
medicine
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the HNMT T314 allele frequency is lower in Chinese population than in American Caucasians. No association can be found in the involvement of HNMT C314T polymorphism in the susceptibility to duodenal ulcer
medicine
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in German Caucasians the association of the HNMT Thr105Ile polymorphism with alcoholism is not replicated, but a congruent association is found between the Ile105 allele and family history of alcoholism supporting the protective role of the Ile105 allele against alcoholism
medicine
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results suggest that alterations of histamine homeostasis are associated with the risk of movement disorders
medicine
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elevation of endogenous histamine by amodiaquine may play a protective role through the regulation of TNF-alpha production in endotoxin-induced hepatic injury mice
degradation
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higher HMT activity seems to be linked to reduced histamine catabolism, percentage of catabolized histamine is not correlated to individual mannitol fluxes and appears to be independent of paracellular permeability