Information on EC 2.1.1.8 - histamine N-methyltransferase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.1.1.8
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RECOMMENDED NAME
GeneOntology No.
histamine N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
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N-methylation
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
histamine degradation
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Histidine metabolism
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:histamine N-tele-methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
9029-80-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + histamine
S-adenosyl-L-homocysteine + Ntau-methylhistamine
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(R)-chloroquine
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50% inhibition at 0.018 mM, liver enzyme, 50% inhibition at 0.0022 mM, brain enzyme
(S)-chloroquine
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50% inhibition at 0.005 mM, liver enzyme, 50% inhibition at 0.007 mM, brain enzyme
1-Methylhistamine
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2-(4-hydroperoxyphenyl)-6-methyl-4H-chromen-4-one
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3,6-dimethyl-2-phenyl-4H-chromen-4-one
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3-bromo-6-chloro-2-phenyl-4H-chromen-4-one
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3-bromo-6-methyl-2-phenyl-4H-chromen-4-one
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3-chloro-6-methyl-2-phenyl-4H-chromen-4-one
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6-chloro-2-phenyl-4H-chromen-4-one
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6-methyl-2-phenyl-4H-chromen-4-one
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8-bromo-6-chloro-2-phenyl-4H-chromen-4-one
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8-bromo-6-methyl-2-phenyl-4H-chromen-4-one
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amodiaquine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
diphenhydramine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
histamine
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0.025-0.1 mM
Metoprine
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potent HNMT inhibitor, occupies the histamine-binding site, thus blocks access to the enzyme’s active site
N-[2(benzhydryloxy)ethyl] N N-dimethylamine
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diphenhydramine, competitive inhibitor
S-adenosylhomocysteine
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SKF 91488
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tacrine
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0042
histamine
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0.0018
S-adenosyl-L-methionine
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additional information
additional information
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000186
amodiaquine
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0.000091
Metoprine
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0.0000382
tacrine
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33000
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x * 33000, deduced from DNA sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 33000, deduced from DNA sequence
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in HMC-1 cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine