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Information on EC 4.1.1.22 - histidine decarboxylase and Organism(s) Homo sapiens

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     4 Lyases
         4.1 Carbon-carbon lyases
             4.1.1 Carboxy-lyases
                4.1.1.22 histidine decarboxylase
IUBMB Comments
A pyridoxal-phosphate protein (in animal tissues). The bacterial enzyme has a pyruvoyl residue as prosthetic group.
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This record set is specific for:
Homo sapiens
Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
DCHS, Decarboxylase, histidine, HDC, HdcA, HisDCase, histamine-forming enzyme, L-Histidine decarboxylase, pyruvoyl-dependent decarboxylase, pyruvoyl-dependent histidine decarboxylase, TOM92, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Decarboxylase, histidine
-
-
-
-
HisDCase
-
-
-
-
L-Histidine decarboxylase
TOM92
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-histidine = histamine + CO2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
-
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
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,4-Dihydroxyphenylalanine
Dopamine + CO2
show the reaction diagram
-
no substate for wild-type. Mutant S354G acquires the ability to decarboxylate 3,4-dihydroxyphenylalanine
-
-
?
L-His
Histamine + CO2
show the reaction diagram
L-histidine
histamine + CO2
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-histidine
histamine + CO2
show the reaction diagram
additional information
?
-
-
induction by phorbol myristate acetate
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epigallocatechin 3-gallate
-
-
4(5)-aminooxymethylimidazole
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O-IMHA, a substrate analogue
4-coumaric acid
-
slight inhibition
alpha-Fluoromethylhistidine
caffeic acid
-
slight inhibition
curcumin
-
slight inhibition
epicatechin
-
-
epicatechin gallate
-
competitive versus L-histidine
epigallocatechin
-
-
epigallocatechin gallate
-
time-dependent inhibition, only under aerobic conditions
epigallocatechin-3-gallate
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EGCG, the inhibitory effect is mediated by blocking the entrance to the catalytic site, therefore, preventing substrate binding
gallic acid
-
slight inhibition
Histidine methyl ester
-
mixed-type inhibition
kaempferol
-
slight inhibition
L-His-L-Phe
-
-
methyl L-histidinate
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the compound is able to block the reaction at the Michaelis complex step in HDC
methylgallate
-
slight inhibition
myricetin
-
-
N-pyridoxyl-L-histidine methyl ester
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60% inhibition at 0.2 mM
phlorizin
-
slight inhibition
pyridoxyl-histidine methyl ester conjugate
-
structure-based inhibitor, binding structure
quercetin
-
slight inhibition
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
Sinapic acid
-
slight inhibition
tellimagrandin II
-
compound isolated from Filipendula ulmaria, non-competitive
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
12-O-tetradecanoylphorbol-13-acetate induces the enzyme
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.13
3,4-dihydroxyphenylalanine
-
mutant S354G, pH 6.8, 37°C
0.27
L-His
-
-
0.09 - 1.45
L-histidine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.29
3,4-dihydroxyphenylalanine
-
mutant S354G, pH 6.8, 37°C
1.73 - 2.01
L-histidine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
9.9
3,4-dihydroxyphenylalanine
-
mutant S354G, pH 6.8, 37°C
1.4 - 20.8
L-histidine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
epicatechin gallate
-
pH 6.8, 37°C, recombinant enzyme, versus L-histidine
0.00046
Histidine methyl ester
-
pH 6.8, 37°C
0.001
rugosin A
-
pH 6.8, 37°C
0.00041
rugosin A methyl ester
-
pH 6.8, 37°C
0.00035
rugosin D
-
pH 6.8, 37°C
0.00094
tellimagrandin II
-
pH 6.8, 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0002
4(5)-aminooxymethylimidazole
Homo sapiens
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0002
-
purified recombinant enzyme from Saccharomyces cerevisiae
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2
-
assay at
6.8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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in basophilic leukemia
Manually annotated by BRENDA team
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substancia nigra and hypothalamus
Manually annotated by BRENDA team
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HDC expression is significantly increased in carcinoma cells
Manually annotated by BRENDA team
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sigmoid and transverse
Manually annotated by BRENDA team
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the tumours are classified based on clinico-pathological criteria
Manually annotated by BRENDA team
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terminal
Manually annotated by BRENDA team
-
cortex
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
immature, low expression level in basophilic leukemia
Manually annotated by BRENDA team
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human oxyntic mucosa contains four major types of neuroendocrine cells: ECL, ghrelin, serotonin and somatostatin cells
Manually annotated by BRENDA team
-
atopic
Manually annotated by BRENDA team
-
HDC expression regulation in histamine producing gastric cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the C-terminus is probably required for sorting the enzyme to the endoplasmic reticulum (ER), after which it can be removed to render the active form of the enzyme located in ER lumen
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
the enzyme belongs to the family of pyridoxal 5'-phosphate-dependent decarboxylases
malfunction
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
DCHS_HUMAN
662
0
74141
Swiss-Prot
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
53000
-
active enzyme form
53000 - 55000
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active enzyme form
54000
-
1 * 54000, enzyme from soluble fraction, SDS-PAGE in absence of 2-mercaptoethanol
74000
-
x * 74000, enzyme from particulate fraction, SDS-PAGE in absence of 2-mercaptoethanol
additional information
-
processing intermediates of about 63 kDa with potential residual activity are observed in some cell types
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 74000, enzyme from particulate fraction, SDS-PAGE in absence of 2-mercaptoethanol
dimer
monomer
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1 * 54000, enzyme from soluble fraction, SDS-PAGE in absence of 2-mercaptoethanol
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
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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
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C179S/C417S
-
double mutation prevents nonspecific polymerization and improves the homogeneity of purified enzyme
C180S/C418S
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mutation facilitates the purification and crystallization of enzyme. Mutant shows Km and kcat values similar to wild-type
D551A/D552A
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mutation in conserved di-aspartate motif. Mutation does not lead to a loss in levels of any of the processed isoforms
DD513A/D514A
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mutation in conserved di-aspartate motif. Mutation does not lead to a loss in levels of any of the processed isoforms
K305G
-
complete loss of activity
S354G
-
mutation at the active site, enlarges the size of the substrate-binding pocket and results in a decreased affinity for histidine, but an acquired ability to bind and act on L-DOPA as a substrate. Mutant exhibits similar absorption spectra as wild-type with two absorption bands at 335 and 425 nm
Y334F
-
complete loss of activity
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
HDC is a short-lived enzyme with a half-life of 1-2 h
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 enzyme forms: 74000 Da and 74000 Da, expression in Escherichia coli
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DNA and amino acid sequence analysis and comparison, intron-exon relationships, phylogenetic analysis, overview
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enzyme expression analysis
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expression in COS7 cell
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expression in Escherichia coli
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gene hdc, located on chromosome 15q21.2, different splicing products, sequence comparisons, regulatory cis elements in the human HDC promoter (TATA, GC, CACC, Sp1 and GATA boxes): two cis-elements are located between the positions -855 and -821 with respect to the transcription start point that regulates the transcription of the HDC in human basophilic cells. Other regulatory elements are located in position -500 and between positions -532 and -497. The HDC promoter also contains a CpG island involved in epigenetic regulation of its expression during the differentiation of histamine-producing cells
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quantitative expression analysis in mast cells of different maturation stage of patients with systemic mastocytosis, overview
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quantitative PCR enzyme expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
12-O-tetradecanoylphorbol-13-acetate induces HDC in mast cells
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both flower buds of Lonicera japonica and chlorogenic acid have inhibitory activities against the expression of 53-kDa HDC and histamine production in human epidermal keratinocytes. Chlorogenic acid shows a weaker effect on histamine production than that of flower buds of Lonicera japonica suggesting that other chemical constituents besides chlorogenic acid might contribute to the inhibitory activities. Chlorogenic acid might have an effect on the histamine production in other cells as well such as mast cells in addition to keratinocytes in the epidermis
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HDC transcription is repressed by Kruppel-like factor 4 (KLF4) interacting at the level of Sp1 binding site, and by the nuclear factors Ying-yang 1 and SREBP-1a that interact with the GC box. The histone acetyl transferases KAT5 (also named as TIP60) and HDAC7 seem to be involved in this mechanisms of KLF4-mediated HDC repression acting as corepressors
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in histamine producing immune cells, HDC expression is modulated by a long list of different stimulus, including lipopolysaccharydes, polypeptides (for instance, neuropeptide P, cytokines), inflammation regulators (for instance, phorbolesters plus dexamethasone), or other compounds (for instance, the intracelular levels of polyamines). Helicobacter pylori infection promotes HDC expression through a signaling pathway involving the trans-elements Rap1 and beta-ra
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ultraviolet B and surfactant exposure induce the expression of histamine-synthesizing enzyme histidine decarboxylase in keratinocytes. Lipopolysaccharide, house dust mite (HDM) extract, and cytokines, which are implicated in allergic inflammation, promote the expression of the enzyme and upregulate histamine levels in keratinocytes
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
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HDC can be used as an immunohistochemical marker for the detection of immature neoplastic mast cells in patients with mast cell-proliferative disorders
drug development
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HDC is a potential target to attenuate histamine production in certain pathological states using structure-based inhibitors, design, synthesis, and test of potentially membrane-permeable pyridoxyl-substrate conjugates as inhibitors for human HDC and modeling of an active site for hHDC, which is compatible with the experimental data, overview
medicine
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loss of HDC is a marker of malignant transformation and dedifferentiation of B-cells infiltrating the skin
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mamune-Sato, R.; Tanno, Y.; Maeyama, K.; Miura, Y.; Takishima, T.; Kishi, K.; Fukuda, T.; Watanabe, T.
Histidine decarboxylase in human basophilic leukemia (KU-812-F) cells
Biochem. Pharmacol.
40
1125-1129
1990
Homo sapiens
Manually annotated by BRENDA team
Yatsunami, K.; Tsuchikawa, M.; Kamada, M.
Expression and characterization of human recombinant parental and mature L-histidine decarboxylase
Methods Find. Exp. Clin. Pharmacol.
17
10-15
1995
Homo sapiens
Manually annotated by BRENDA team
Tetlow, L.C.; Woolley, D.E.
Immunolocalization of histamine and histidine decarboxylase in chondrocytes of arthritic cartilage
Inflamm. Res.
53
S21-S22
2004
Homo sapiens
-
Manually annotated by BRENDA team
Tetlow, L.C.; Woolley, D.E.
Histamine, histamine receptors (H(1) and H(2)), and histidine decarboxylase expression by chondrocytes of osteoarthritic cartilage: an immunohistochemical study
Rheumatol. Int.
26
173-178
2005
Homo sapiens
Manually annotated by BRENDA team
Wu, F.; Yu, J.; Gehring, H.
Inhibitory and structural studies of novel coenzyme-substrate analogs of human histidine decarboxylase
FASEB J.
22
890-897
2007
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Krauth, M.T.; Agis, H.; Aichberger, K.J.; Simonitsch-Klupp, I.; Muellauer, L.; Mayerhofer, M.; Boehm, A.; Horny, H.P.; Valent, P.
Immunohistochemical detection of histidine decarboxylase in neoplastic mast cells in patients with systemic mastocytosis
Hum. Pathol.
37
439-447
2006
Homo sapiens
Manually annotated by BRENDA team
Nitta, Y.; Kikuzaki, H.; Ueno, H.
Food components inhibiting recombinant human histidine decarboxylase activity
J. Agric. Food Chem.
55
299-304
2007
Homo sapiens
Manually annotated by BRENDA team
Okigami, H.; Ueno, H.
Bioinformatic study on histidine decarboxylase
J. Biol. Macromol.
6
11-27
2006
Aplysia californica (Q86BW8), Arabidopsis thaliana (Q9MA74), Clostridium tetani (Q894Q7), Drosophila melanogaster (Q05733), Gloeobacter violaceus (Q7NIG4), Homo sapiens (P19113), Klebsiella aerogenes (P28577), Mesorhizobium loti (Q98A07), Morganella morganii (P05034), Mus musculus (Q7TMW5), Oryza sativa (Q8RV06), Photobacterium phosphoreum (Q846V2), Pseudomonas fluorescens (P95477), Raoultella planticola (P28578), Rattus norvegicus (P16453), Solanum lycopersicum (P54772), Vibrio anguillarum (Q56581), Vibrio anguillarum (Q79JY8)
-
Manually annotated by BRENDA team
Brew, O.; Lakasing, L.; Sullivan, M.
Differential activity of histidine decarboxylase in normal and pre-eclamptic placentae
Placenta
28
585-587
2007
Homo sapiens
Manually annotated by BRENDA team
Maintz, L.; Schwarzer, V.; Bieber, T.; van der Ven, K.; Novak, N.
Effects of histamine and diamine oxidase activities on pregnancy: a critical review
Hum. Reprod. Update
14
485-495
2008
Homo sapiens
Manually annotated by BRENDA team
Varkonyi, J.; Karadi, I.; Szocs, K.; Sugar, I.; Sapi, Z.; Marschalko, M.; Pallinger, E.; Darvas, Z.; Falus, A.
Loss of histidine decarboxylase as a marker of malignant transformation and dedifferentiation of B-cells infiltrating the skin. A case report of a therapy-resistant multiple myeloma complicated by skin infiltration
Acta Oncol.
47
458-461
2008
Homo sapiens
Manually annotated by BRENDA team
Li, Z.; Liu, J.; Tang, F.; Liu, Y.; Waldum, H.L.; Cui, G.
Expression of non-mast cell histidine decarboxylase in tumor-associated microvessels in human esophageal squamous cell carcinomas
APMIS
116
1034-1042
2008
Homo sapiens
Manually annotated by BRENDA team
Medina, V.; Croci, M.; Crescenti, E.; Mohamad, N.; Sanchez-Jimenez, F.; Massari, N.; Nunez, M.; Cricco, G.; Martin, G.; Bergoc, R.; Rivera, E.S.
The role of histamine in human mammary carcinogenesis: H3 and H4 receptors as potential therapeutic targets for breast cancer treatment
Cancer Biol. Ther.
7
28-35
2008
Homo sapiens
Manually annotated by BRENDA team
Andersson, C.K.; Mori, M.; Bjermer, L.; Loefdahl, C.G.; Erjefaelt, J.S.
Novel site-specific mast cell subpopulations in the human lung
Thorax
64
297-305
2009
Homo sapiens
Manually annotated by BRENDA team
Wu, F.; Christen, P.; Gehring, H.
A novel approach to inhibit intracellular vitamin B6-dependent enzymes: proof of principle with human and plasmodium ornithine decarboxylase and human histidine decarboxylase
FASEB J.
25
2109-2122
2011
Homo sapiens
Manually annotated by BRENDA team
Komori, H.; Nitta, Y.; Ueno, H.; Higuchi, Y.
Purification, crystallization and preliminary X-ray analysis of human histidine decarboxylase
Acta Crystallogr. Sect. F
68
675-677
2012
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Fennell, L.M.; Fleming, J.V.
Differential processing of mammalian L-histidine decarboxylase enzymes
Biochem. Biophys. Res. Commun.
445
304-309
2014
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Nitta, Y.; Kikuzaki, H.; Azuma, T.; Ye, Y.; Sakaue, M.; Higuchi, Y.; Komori, H.; Ueno, H.
Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylase
Food Chem.
138
1551-1556
2013
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Komori, H.; Nitta, Y.; Ueno, H.; Higuchi, Y.
Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase
J. Biol. Chem.
287
29175-29183
2012
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Gutowska-Owsiak, D.; Greenwald, L.; Watson, C.; Selvakumar, T.A.; Wang, X.; Ogg, G.S.
The histamine-synthesizing enzyme histidine decarboxylase is upregulated by keratinocytes in atopic skin
Br. J. Dermatol.
171
771-778
2014
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Fernandes, H.S.; Ramos, M.J.; Cerqueira, N.M.F.S.A.
The catalytic mechanism of the pyridoxal-5'-phosphate-dependent enzyme, histidine decarboxylase a computational study
Chemistry
23
9162-9173
2017
Homo sapiens (P19113)
Manually annotated by BRENDA team
Inami, Y.; Matsui, Y.; Hoshino, T.; Murayama, C.; Norimoto, H.
Inhibitory activity of the flower buds of Lonicera japonica Thunb. against histamine production and L-histidine decarboxylase in human keratinocytes
Molecules
19
8212-8219
2014
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Sanchez-Jimenez, F.; Pino-Angeles, A.; Rodriguez-Lopez, R.; Morales, M.; Urdiales, J.L.
Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks biomedical implications
Pharmacol. Res.
114
90-102
2016
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
Tsolakis, A.V.; Grimelius, L.; Granerus, G.; Stridsberg, M.; Falkmer, S.E.; Janson, E.T.
Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours
World J. Gastroenterol.
21
13240-13249
2015
Homo sapiens, Homo sapiens (P19113)
Manually annotated by BRENDA team
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