Information on EC 4.1.1.22 - Histidine decarboxylase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
4.1.1.22
-
RECOMMENDED NAME
GeneOntology No.
Histidine decarboxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-histidine = histamine + CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
histamine biosynthesis
-
-
histidine metabolism
-
-
Histidine metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
L-histidine carboxy-lyase (histamine-forming)
A pyridoxal-phosphate protein (in animal tissues). The bacterial enzyme has a pyruvoyl residue as prosthetic group.
CAS REGISTRY NUMBER
COMMENTARY hide
9024-61-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
33% of the tested strains are positive for histidine decarboxylase
-
-
Manually annotated by BRENDA team
-
TREMBL
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain MB31
SwissProt
Manually annotated by BRENDA team
strain MB31
SwissProt
Manually annotated by BRENDA team
strain 0006
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
fragment; strain LTH2076
UniProt
Manually annotated by BRENDA team
fragment; strain LTH2076
UniProt
Manually annotated by BRENDA team
i.e. Mesorhizobium loti
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain AM-15
-
-
Manually annotated by BRENDA team
strain JCM1672T
SwissProt
Manually annotated by BRENDA team
BDF1 mice
-
-
Manually annotated by BRENDA team
no activity in Buttiauxella sp.
-
-
-
Manually annotated by BRENDA team
no activity in Cedecea sp.
-
-
-
Manually annotated by BRENDA team
no activity in Citrobacter amalonaticus
-
-
-
Manually annotated by BRENDA team
no activity in Citrobacter farmeri
-
-
-
Manually annotated by BRENDA team
no activity in Citrobacter koseri
-
-
-
Manually annotated by BRENDA team
no activity in Citrobacter sedlakii
-
-
-
Manually annotated by BRENDA team
no activity in Edwardsiella tarda
-
-
-
Manually annotated by BRENDA team
no activity in Enterobacter cloacae
-
-
-
Manually annotated by BRENDA team
no activity in Escherichia coli
-
-
-
Manually annotated by BRENDA team
no activity in Ewingella americana
-
-
-
Manually annotated by BRENDA team
no activity in Hafnia alvei
-
-
-
Manually annotated by BRENDA team
no activity in Klebsiella oxytoca
-
-
-
Manually annotated by BRENDA team
no activity in Klebsiella pneumoniae
-
-
-
Manually annotated by BRENDA team
no activity in Kluyvera sp.
-
-
-
Manually annotated by BRENDA team
no activity in Leclercia adecarboxylata
-
-
-
Manually annotated by BRENDA team
no activity in Leminorella sp.
-
-
-
Manually annotated by BRENDA team
no activity in Moellerella wisconsensis
-
-
-
Manually annotated by BRENDA team
no activity in Pantoea sp.
-
-
-
Manually annotated by BRENDA team
no activity in Proteus mirabilis
-
-
-
Manually annotated by BRENDA team
no activity in Proteus penneri
-
-
-
Manually annotated by BRENDA team
no activity in Proteus vulgaris
-
-
-
Manually annotated by BRENDA team
no activity in Providencia sp.
-
-
-
Manually annotated by BRENDA team
no activity in Rahnella aquatilis
-
-
-
Manually annotated by BRENDA team
no activity in Raoultella terrigena
-
-
-
Manually annotated by BRENDA team
no activity in Salmonella sp.
-
-
-
Manually annotated by BRENDA team
no activity in Serratia marcescens
-
-
-
Manually annotated by BRENDA team
no activity in Shigella sp.
-
-
-
Manually annotated by BRENDA team
no activity in Yersinia enterocolitica
-
-
-
Manually annotated by BRENDA team
no activity in Yersinia pseudotuberculosis
-
-
-
Manually annotated by BRENDA team
ssp. japonica
TREMBL
Manually annotated by BRENDA team
strain JCM 8968, gene hdc
UniProt
Manually annotated by BRENDA team
strain MB36
SwissProt
Manually annotated by BRENDA team
strain NBRC 13896; strain NBRC 13896, gene hdc
UniProt
Manually annotated by BRENDA team
strain YS4-7; strain YS4-7, gene hdc
UniProt
Manually annotated by BRENDA team
strain AU34
SwissProt
Manually annotated by BRENDA team
strain AU34
SwissProt
Manually annotated by BRENDA team
strain 8433
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
strain IFIJ12
UniProt
Manually annotated by BRENDA team
strain IFIJ12
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
strain H
UniProt
Manually annotated by BRENDA team
strain H
UniProt
Manually annotated by BRENDA team
JCM 10006T
-
-
Manually annotated by BRENDA team
strain JCM10006
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
the enzyme and its product, histamine, are involved in multiple inflammatory diseases, atherosclerosis, some neurological and neuroendocrine diseases, osteroporosis, fertility, and several types of neoplasia
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-Methylhistidine
1-Methylhistamine
show the reaction diagram
-
very poor substrate
-
-
-
2-Thiolhistidine
1-Thiolhistamine
show the reaction diagram
-
very poor substrate
-
-
-
3,4-Dihydroxyphenylalanine
Dopamine + CO2
show the reaction diagram
-
no substate for wild-type. Mutant S354G acquires the ability to decarboxylate 3,4-dihydroxyphenylalanine
-
-
?
3-Methylhistidine
2-Methylhistamine
show the reaction diagram
-
very poor substrate
-
-
-
beta-(1,2,4-Triazole-3)-Ala
?
show the reaction diagram
-
very poor substrate
-
-
-
beta-(Pyridyl-2)-Ala
?
show the reaction diagram
beta-(Thiazole-2)-Ala
?
show the reaction diagram
-
very poor substrate
-
-
-
L-His
Histamine + CO2
show the reaction diagram
L-histidin
histamine + CO2
show the reaction diagram
-
-
-
?
L-histidine
histamine + CO2
show the reaction diagram
Npi-Methylhistidine
?
show the reaction diagram
additional information
?
-
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
L-histidin
histamine + CO2
show the reaction diagram
-
-
-
?
L-histidine
histamine + CO2
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
Pyruvoyl group
-
dependent on
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CaCl2
-
maximal activity is observed only in the presence of high concentrations of various salts: KCl, NaCl, NaBr, K2SO4, CaCl2 or MgCl2
Fe3+
-
0.1 mM, enhances activity by 7-8%
K2SO4
-
maximal activity is observed only in the presence of high concentrations of various salts: KCl, NaCl, NaBr, K2SO4, CaCl2 or MgCl2
KCl
-
maximal activity is observed only in the presence of high concentrations of various salts: KCl, NaCl, NaBr, K2SO4, CaCl2 or MgCl2
MgCl2
-
maximal activity is observed only in the presence of high concentrations of various salts: KCl, NaCl, NaBr, K2SO4, CaCl2 or MgCl2
Mn2+
-
0.1 mM, enhances activity by 7-8%
NaBr
-
maximal activity is observed only in the presence of high concentrations of various salts: KCl, NaCl, NaBr, K2SO4, CaCl2 or MgCl2
NaCl
-
maximal activity is observed only in the presence of high concentrations of various salts: KCl, NaCl, NaBr, K2SO4, CaCl2 or MgCl2
additional information
-
constitutive and inducible enzyme show optimal activity in absence of NaCl
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epigallocatechin 3-gallate
-
-
(S)-alpha-fluoromethylhistidine
-
0.001 mM, complete inhibition
2-Hydrazino-3-(4-imidazolyl)propionic acid
-
-
2-Hydroxy-5-nitrobenzylbromide
-
-
4-coumaric acid
-
slight inhibition
5,5'-dithiobis(2-nitrobenzoate)
-
-
alpha-Fluoromethylhistidine
alpha-Methylhistidine
caffeic acid
-
slight inhibition
carnosine
Citric acid
Co(NO3)2
-
slight
Co2+
-
0.1 mM, 20% decrease of activity
Cu2+
-
0.1 mM, strong inhibition
curcumin
-
slight inhibition
Cyanoborohydride
D-fructose
D-glucose
dithiothreitol
epicatechin
-
-
Epicatechin gallate
-
competitive versus L-histidine
epigallocatechin
-
-
epigallocatechin gallate
-
time-dependent inhibition, only under aerobic conditions
epigallocatechin-3-gallate
epsilon-N-Pyridoxyllysine
-
-
gallic acid
-
slight inhibition
guanidine
-
-
Hg2+
-
0.1 mM, strong inhibition
histamine
Histidine methyl ester
Hydrazine sulfate
imidazole
Imidazoleacetic acid
-
-
kaempferol
-
slight inhibition
KCl
-
50% inhibition at 1.5 M
KCN
-
non-competitive
L-Citric acid
-
19% hdc gene expression at 0.8 g/l
L-Fructose
-
46% hdc gene expression at 50 g/l
L-Glucose
-
22% hdc gene expression at 50 g/l
L-His-L-Phe
-
-
L-Histidine ethyl ester
-
-
L-histidine methyl ester
-
-
L-Malic acid
-
26% hdc gene expression at 4 g/l
malic acid
methylgallate
-
slight inhibition
myricetin
-
-
N-pyridoxyl-L-histidine methyl ester
-
60% inhibition at 0.2 mM
Ni2+
-
0.1 mM, 15% decrease of activity
p-hydroxymercuribenzoate
-
-
phlorizin
-
slight inhibition
pyridoxal 5'-phosphate
-
non-competitive inhibition with respect to His, at high concentrations
pyridoxyl-histidine methyl ester conjugate
-
structure-based inhibitor, binding structure
quercetin
-
slight inhibition
reduced glutathione
-
-
rosmarinic acid
-
-
rugosin A
-
compound isolated from Filipendula ulmaria, non-competitive
rugosin A methyl ester
-
compound isolated from Filipendula ulmaria, non-competitive
rugosin D
-
compound isolated from Filipendula ulmaria, non-competitive
Semicarbazide
-
-
Shoyuflavones
Sinapic acid
-
slight inhibition
tellimagrandin II
-
compound isolated from Filipendula ulmaria, non-competitive
Urocanic acid
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Butyrate
-
highly activating for the wild-type enzyme
C/EBPbeta
-
essential for the HDC induction
-
ethanol
gastrin
-
increase of steady-state levels of 6 HDC isoforms
HdcB
-
HdcB catalyses the maturation of pyruvoyl-dependent histidine decarboxylase by cleavage of the proenzyme which results in the formation of the pyruvoyl prosthetic group
-
lipopolysaccharide
-
excreted from Escherichia coli after oral infection, stimulates the enzyme in dental pulp and gingiva, tissue-specific effects, oveview
monosodium urate
monosodium urate crystals injected into the air pouch lead to a highly upregulated mRNA level of HDC
-
pyridoxal 5'-phosphate
pyruvate
SH-groups
-
wild type and mutant enzyme each contain two SH groups per alpha-chain
toluene 2,4-diisocyanate
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.13
3,4-dihydroxyphenylalanine
-
mutant S354G, pH 6.8, 37C
5.8
alpha-methyl-DL-His
-
-
0.078 - 35
L-His
0.09 - 100
L-histidine
additional information
additional information
-
between pH 6 and pH 9 the Km-value for L-His declines from 1 mM to about 0.01 mM
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.29
3,4-dihydroxyphenylalanine
Homo sapiens
-
mutant S354G, pH 6.8, 37C
1.73 - 2.01
L-histidine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9.9
3,4-dihydroxyphenylalanine
Homo sapiens
-
mutant S354G, pH 6.8, 37C
1782
1.4 - 20.8
L-histidine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
Epicatechin gallate
-
pH 6.8, 37C, recombinant enzyme, versus L-histidine
0.00046
Histidine methyl ester
-
pH 6.8, 37C
0.001
rugosin A
-
pH 6.8, 37C
0.00041
rugosin A methyl ester
-
pH 6.8, 37C
0.00035
rugosin D
-
pH 6.8, 37C
0.00094
tellimagrandin II
-
pH 6.8, 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00000014
-
HDC activity in cultured brain microvascular endothelial cells
0.0002
-
purified recombinant enzyme from Saccharomyces cerevisiae
0.75
-
-
0.8
-
-
17.26
-
-
136
-
purified recombinant enzyme
143
purified recombinant enzyme
144
purified recombinant enzyme
166
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.7
-
assay at
7.2 - 8
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.5 - 8
-
50% of maximal activity at pH 3.5
4
about 50% of maximum activity
4.2
83% of maximum activity
4.5 - 8.5
5.5 - 8.5
rapid loss of activity below pH 5.5; rapid loss of activity below pH 5.5
5.5 - 8
-
pH 5.5: about 35% of maximal activity, pH 8.0: about 10% of maximal activity, membrane-bound enzyme; pH 5.5: about 50% of maximal activity, pH 8.0: about 40% of maximal activity, soluble enzyme
6 - 7.6
-
pH 6.0: about 50% of maximal activity, pH 7.6: about 40% of maximal activity
6.5
-
inducible enzyme
7
sharp decline in activiy above
8
18% of maximum activity
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 50
47 - 60
-
47C: about 50% of maximal activity, 60C: about 75% of maximal activity, no activity detectable at 65C
83
83% of maximum activity
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.7 - 4.8
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
the posterodorsal medial amygdala has high levels of histidine decarboxylase
Manually annotated by BRENDA team
-
in basophilic leukemia
Manually annotated by BRENDA team
-
HDC expression is significantly increased in carcinoma cells
Manually annotated by BRENDA team
-
in the acute phase of infection of mice infected with Leishmania major, detected in both strains the resistant C57BL/6 and the susceptible BALB/c. Only susceptible mice known to be unable to control parasite dissemination show induction of histidine decarboxylase in their distant periaortic lymph nodes as well. During the chronic phase of infection only the heavily parasitized organs of BALB/c mice show high expression of histidine decarboxylase gene
Manually annotated by BRENDA team
-
immature, low expression level in basophilic leukemia
Manually annotated by BRENDA team
-
histidine decarboxylase is induced upon infiltration of polymorphonuclear leukocytes into mouse peritoneal cavity. Histamine is synthesized by the enzyme attached to the granule membrane of polymorphonuclear leukocytes
Manually annotated by BRENDA team
-
ear skin
Manually annotated by BRENDA team
-
in enterochromaffin-like cell, not in G cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
acrosomes of spermatids and spermatozoa
-
Manually annotated by BRENDA team
-
N-terminal membrane localization of the precursor 74-kDa form of the enzyme, which has neither an amino terminal signal sequence nor a hydrophobic membrane anchor, but a large C-terminal cytosolic portion, overview
Manually annotated by BRENDA team
additional information
-
granules of elicited mouse polymorphonuclear leukocytes. Histamine is synthesized by the enzyme attached to the granule membrane of polymorphonuclear leukocytes
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Lactobacillus sp. (strain 30a)
Lactobacillus sp. (strain 30a)
Lactobacillus sp. (strain 30a)
Lactobacillus sp. (strain 30a)
Lactobacillus sp. (strain 30a)
Lactobacillus sp. (strain 30a)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34200
pi chain of HDC
95000
-
enzyme form 1, 2 and 3, gel filtration
100000
-
gel filtration
110000
113400
-
gel filtration
115000
-
native PAGE
121000
gel filtration
170000
-
gel filtration
190000
-
-
208000
-
equilibrium sedimentation
210000
-
gel filtration
258000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dodecamer
heterodimer
-
1 * 24000 + 1 * 12000, mature enzyme, SDS-PAGE
hexamer
homodimer
-
-
monomer
-
1 * 54000, enzyme from soluble fraction, SDS-PAGE in absence of 2-mercaptoethanol
multimer
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
core domain, to 1.8 A resolution. Three dimers per asymmetric unit. Molecular replacement carried out using the AroDC structure as a model
-
in complex with the inhibitor histidine methyl ester, to 1.8 A resolution. Cofactor pyridoxal 5'-phosphate is located in the large domain. The pyridine ring of pyridoxal 5'-phosphate is sandwiched between the methyl group of Ala275 and the imidazole ring of His194. Residue Ser354 is a key residue for substrate specificity
-
crystal structure at 3.0 A resolution
-
crystal structure of active HDC at pH 4.8 at 2.5 A resolution, crystal structure of less active HDC at pH 8.0 at 2.7 A resolution, crystals are grown at room temperatur by hanging-drop vapor diffusion, drops contain 0.004 ml HDC at 12.5 mg/ml, 0.001 ml n-dodecyl-beta-D-maltoside and 0.005 ml precipitant solution from the well containing 25% polyethylene glycol 400, 8% polyethylene glycol 400, 100 mM Tris pH 8.0, and 100 mM sodium acetate, enzyme activity is regulated by pH-induced structural changes
modeling of complex with inhibitor epigallocatechin-3-gallate. The presence of epigallocatechin-3-gallate contiguous to the active site entrance leads to the movement of several residues in the active site. Epigallocatechin-3-gallate occludes the entrance channel to the enzyme active site and establishes new interactions with residues in the active site. These residues turn outward when the active site collapses
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE