Information on EC 4.3.1.3 - histidine ammonia-lyase

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

EC NUMBER
COMMENTARY hide
4.3.1.3
-
RECOMMENDED NAME
GeneOntology No.
histidine ammonia-lyase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-histidine = urocanate + NH3
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Deamination
-
-
elimination
elimination of NH3
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
histidine metabolism
-
-
Histidine metabolism
-
-
L-histidine degradation I
-
-
L-histidine degradation II
-
-
L-histidine degradation III
-
-
L-histidine degradation VI
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
L-histidine ammonia-lyase (urocanate-forming)
This enzyme is a member of the aromatic amino acid lyase family, other members of which are EC 4.3.1.23 (tyrosine ammonia-lyase), EC 4.3.1.24 (phenylalanine ammonia-lyase) and EC 4.3.1.25 (phenylalanine/tyrosine ammonia-lyase). The enzyme contains the cofactor 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO), which is common to this family [4]. This unique cofactor is formed autocatalytically by cyclization and dehydration of the three amino-acid residues alanine, serine and glycine [5]. This enzyme catalyses the first step in the degradation of histidine and the product, urocanic acid, is further metabolized to glutamate [2,3].
CAS REGISTRY NUMBER
COMMENTARY hide
9013-75-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Achromobacter liquidum
IAM 1667
-
-
Manually annotated by BRENDA team
Achromobacter liquidum IAM 1667
IAM 1667
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Bacillus subtilis Marburg 168
Marburg 168
-
-
Manually annotated by BRENDA team
W23G
-
-
Manually annotated by BRENDA team
CCAP 11/32A
-
-
Manually annotated by BRENDA team
CCAP 11/32A
-
-
Manually annotated by BRENDA team
sunflower
-
-
Manually annotated by BRENDA team
2362
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Salmo gairdnerii Richardson
-
-
Manually annotated by BRENDA team
A.3.12
-
-
Manually annotated by BRENDA team
A.3.12
-
-
Manually annotated by BRENDA team
PRS1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
spinach
-
-
Manually annotated by BRENDA team
NRRL B-2682
-
-
Manually annotated by BRENDA team
toad
-
-
-
Manually annotated by BRENDA team
soil samples from the Ap horizont of a black chernozemic soil, Typic Cryoboroll, under grass, dominantly Festuca rubra
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Baldi, Giza2; Romi, Equadolze
-
-
Manually annotated by BRENDA team
Xenopus (Silurana) tropicalis
two duplicated HAL genes, HAL1 and HAL2, exist in this organism
SwissProt
Manually annotated by BRENDA team
two duplicated HAL genes, HAL1 and HAL2, exist in this organism
UniProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-fluorohistidine
2-fluorourocanate + NH3
show the reaction diagram
-
-
-
?
4-fluoro-DL-histidine
4-fluorourocanate + NH3
show the reaction diagram
-
very poor substrate
-
r
4-fluorohistidine
4-fluorourocanate + NH3
show the reaction diagram
-
-
-
-
?
4-nitro-L-histidine
4-nitrourocanate + NH3
show the reaction diagram
-
-
-
-
?
DL-histidine
urocanate + NH3
show the reaction diagram
-
-
-
?
L-aspartate
fumarate + NH3
show the reaction diagram
-
-
-
-
?
L-histidine
trans-urocanic acid + NH3
show the reaction diagram
L-histidine
urocanate + NH3
show the reaction diagram
L-histidine methyl ester
urocanate methyl ester
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-histidine
trans-urocanic acid + NH3
show the reaction diagram
L-histidine
urocanate + NH3
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
AMP
-
0.016 mM, maximal activity
vitamin B12
-
0.0033 mM, maximal activity
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
activates at a concentration of 0.1 mM
Fe2+
-
required for optimal activity
additional information
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-3-(1-benzofuran-2-yl)prop-2-enoic acid
-
-
(2E)-3-(1-benzofuran-3-yl)prop-2-enoic acid
-
-
(2E)-3-(1-benzothiophen-2-yl)prop-2-enoic acid
-
-
(2E)-3-(1-benzothiophen-3-yl)prop-2-enoic acid
-
-
(2E)-3-(1-methyl-1H-indol-3-yl)prop-2-enoic acid
-
-
(2E)-3-(1H-indol-3-yl)prop-2-enoic acid
-
-
(2E)-3-(3-methylfuran-2-yl)prop-2-enoic acid
-
-
(2E)-3-(3-methylthiophen-2-yl)prop-2-enoic acid
-
-
(2E)-3-furan-2-ylprop-2-enoic acid
-
-
(2E)-3-thiophen-2-ylprop-2-enoic acid
-
-
1,2,4-triazole-DL-alanine
Achromobacter liquidum
-
competitive
1-amino-2-imidazol-4'-ylethylphosphonic acid
-
reversible, competitive, 1 mM: complete inhibition
1-Methyltryptophan
-
-
2,3 butanedione
-
-
2-mercaptoethanol
-
inhibition at concentrations above 10 mM, reversed by addition of metal ion
2-methyl-DL-histidine
Achromobacter liquidum
-
competitive
2-thiazolyl-DL-alanine
Achromobacter liquidum
-
competitive
3-(1-benzofuran-2-yl)alanine
-
-
3-(1-benzofuran-3-yl)alanine
-
-
3-(1-benzothiophen-2-yl)alanine
-
-
3-(1-benzothiophen-3-yl)alanine
-
-
3-(3-methylthiophen-2-yl)alanine
-
-
3-furan-2-ylalanine
-
-
3-methyl-L-histidine
Achromobacter liquidum
-
competitive
3-thiophen-2-ylalanine
-
-
5,5'-dithiobis(2-nitrobenzoic acid)
8-methoxypsoralen
-
noncompetitive. Irradiation of 8-methoxypsoralen with broadband UVA and broadband UVA/UVB results in uncompetitive inhibition due to psoralen-oxidized photoproducts
all-trans retinoic acid
-
1 microM suppresses histidase expression almost completely, levels of histidase mRNA expression in the presence of all-trans retinoic acid are significantly lower on day 2 of post-confluence and at all later time points during keratinocyte differentiation
alpha-methyl-DL-histidine
Achromobacter liquidum
-
competitive
Ba2+
Achromobacter liquidum
-
1 mM
beta-imidazole lactic acid
Achromobacter liquidum
-
competitive
biguanide
-
-
bisulfite
Co3+
-
0.1 mM, 95% inhibition
Cu2+
-
0.1 mM, 70% inhibition
cyanide
-
50 mM histidinol phosphate, 5 mM L-histidine and 5 mM Mn2+ protects
D-alpha-hydrazinohistidine
-
competitive
D-alpha-hydrazinoimidazolylpropionic acid
D-Cysteine
-
in the presence of Cd2+
D-histidine
dithiothreitol
DL-alpha-hydrazinoimidazolylpropionic acid
-
70% irreversible inactivation in vivo
DL-pyrazolyl-3-alanine
-
5.0 mM
Fe2+
-
0.1 mM, 60% inhibition
formyl-L-histidine
Achromobacter liquidum
-
competitive
glycine
H2O2
Achromobacter liquidum
-
-
histidinol phosphate
-
competitive
hydroxylamine
-
-
hydroxymethylimidazole
Achromobacter liquidum
-
competitive
-
imidazol-3-ylpyruvate
-
uncompetitive
-
imidazole
Achromobacter liquidum
-
noncompetitive
interleukin-1alpha
-
treatment of IL-1a reduces histidase expression, the suppressive effect can be reverted by concomitant treatment with interleukin-1alpha receptor antagonist
-
L-1-methylhistidine
-
5.0 mM
L-alanine
-
5.0 mM
L-alpha-hydrazinoimidazolylpropionic acid
-
competitive
-
L-cysteine
L-histidine hydrazide
Achromobacter liquidum
-
noncompetitive
L-histidine hydroxamate
L-histidinemethyl ester
L-Histidinol
L-homocysteine
-
irreversible in the presence of O2 and high pH
L-N-gamma-methylhistidine
-
weak competitive
L-tyrosine
-
heat-purified enzyme, at low concentrations, pH 7-8
methylglyoxal
-
-
N-acetyl-L-histidine
-
5.0 mM
N-ethylmaleimide
-
1 mM, partial
Nitromethane
norhistidine
-
-
-
O2
-
irreversible
p-fluoro-L-histidine
p-hydroxyphenylpyruvate
-
heat-purified enzyme, at low concentrations, pH 7-8
p-mercuribenzoate
p-nitro-L-histidine
-
competitive
-
Pb2+
Achromobacter liquidum
-
1 mM
Phenylglyoxal
-
protection by histidinol phosphate
phenylhydrazine
-
-
Sodium diphosphate
-
-
TGF-alpha
-
most pronounced effect, leads to almost complete suppression of histidase expression
-
TNF-alpha
-
suppresses the expression of histidase
-
tryptophan
-
-
Urocanate
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
dithiothreitol
-
activates
estrogen
-
transcriptional activator of histidase expression
glucocorticoid
-
transcriptional activator of histidase expression
-
sulfhydryl compounds
additional information
-
detection of increased trans-urocanic acid levels in the epidermis of patients with psoriasis and in UV-treated epidermis indicates that epidermal histidase may be subject to regulation by endogenous and exogenous factors; expression of histidase strongly increases at the mRNA and protein levels during differentiation of primary keratinocytes in vitro; treatment of keratinocytes with UVA and UVB does not significantly change the expression level of histidase
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
20
2-fluorohistidine
-
-
1.25 - 6.4
4-fluoro-DL-histidine
5
4-fluorourocanate
-
-
2.7 - 10
DL-histidine
0.2 - 20
L-histidine
3 - 100
Urocanate
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
86 - 255
L-histidine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.056
(2E)-3-(1-benzofuran-2-yl)prop-2-enoic acid
-
competitive inhibition
0.023
(2E)-3-(1-benzofuran-3-yl)prop-2-enoic acid
-
competitive inhibition
0.039
(2E)-3-(1-benzothiophen-2-yl)prop-2-enoic acid
-
competitive inhibition
0.053
(2E)-3-(1-benzothiophen-3-yl)prop-2-enoic acid
-
competitive inhibition
0.026
(2E)-3-(1-methyl-1H-indol-3-yl)prop-2-enoic acid
-
competitive inhibition
0.015
(2E)-3-(1H-indol-3-yl)prop-2-enoic acid
-
competitive inhibition
0.018
(2E)-3-(3-methylfuran-2-yl)prop-2-enoic acid
-
competitive inhibition
0.04
(2E)-3-(3-methylthiophen-2-yl)prop-2-enoic acid
-
competitive inhibition
0.033
(2E)-3-furan-2-ylprop-2-enoic acid
-
competitive inhibition
0.041
(2E)-3-thiophen-2-ylprop-2-enoic acid
-
competitive inhibition
0.031
1-Methyltryptophan
-
mixed inhibition
0.025
3-(1-benzofuran-2-yl)alanine
-
competitive inhibition
0.067
3-(1-benzofuran-3-yl)alanine
-
competitive inhibition
0.083
3-(1-benzothiophen-2-yl)alanine
-
competitive inhibition
0.082
3-(1-benzothiophen-3-yl)alanine
-
competitive inhibition
0.098
3-(3-methylthiophen-2-yl)alanine
-
competitive inhibition
0.139
3-furan-2-ylalanine
-
competitive inhibition
0.101
3-thiophen-2-ylalanine
-
competitive inhibition
0.001
EDTA
-
-
1.72
norhistidine
-
mixed inhibition
-
0.05
tryptophan
-
mixed inhibition
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.3427
-
native enzyme
1.2
-
0.1 mM Ca2+, oxidized enzyme
2.3
-
0.1 mM Mn2+, oxidized enzyme
2.8
-
0.1 mM Fe2+, oxidized enzyme
3.4
-
37C, pH 9.0, 3.3 mM L-histidine
4.3
-
0.1 mM Zn2+, oxidized enzyme
6.2
-
0.1 mM Ca2+, reduced enzyme
7
-
0.1 mM Fe2+ or 0.1 mM Zn2+, reduced enzyme
9.1
-
0.1 mM Mn2+, reduced enzyme
63
Achromobacter liquidum
-
-
70.4
-
cloned enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.2
Achromobacter liquidum
-
-
8.5 - 9.1
-
maximal activity between
9.3
-
activity assay
additional information
-
the activity optimum of histidase near pH 7 suggests that histidase is active predominantly in the lower, less acidic portion of the stratum corneum
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 10
-
inactive below pH 6.5, 75% of maximal activity at pH 10.0
7 - 10
-
pH 7.0: 10% of maximal activity, pH 10: about 50% of maximal activity
7.2 - 9.4
Achromobacter liquidum
-
half-maximal activity at pH 7.2 and at pH 9.4
8.1 - 9.9
-
50% of maximal activity at pH 8.1 and pH 9.9
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 35
-
maximal activity between
50
Achromobacter liquidum
-
-
60 - 65
-
maximal activity between
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
-10 - 60
-
-10C: pH 9.2, assay mixture containing 21% dimethylsulfoxide remains liquid, activity is 5,8% of the activity at 30C, 60C: 20% of maximal activity
additional information
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
i.e. Auerbach's plexus; intramuscular plexus
Manually annotated by BRENDA team
-
adjacent to portal triads
Manually annotated by BRENDA team
-
epidermal
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
152400
-
gel filtration
189000
-
sucrose density gradient centrifugation
190000
-
sedimentation equilibrium
200000
203000
-
disc gel electrophoresis
204000
toad
-
sucrose density gradient centrifugation
210000
218000
-
sucrose density gradient centrifugation
220000
226000
-
sucrose density gradient centrifugation
243000
-
sucrose density gradient centrifugation
additional information
-
-
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 71800, SDS-PAGE
tetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
-
Achromobacter liquidum
-
construction of enzyme structure with a closed active site by modifying the HAL structure including the L-cysteine inhibitor by replacement of the 39-80 loop containing the catalytically essential Tyr53, in every subunit of the homotetrameric enzyme. The most plausible reaction pathway involves the N-3,5-dihydro-5-methylidene-4H-imidazol-4-one intermediate structure in which the L-histidine substrate is covalently bound to the N-3,5-dihydro-5-methylidene-4H-imidazol-4-one prosthetic group of the apoenzyme via the amino group. Zn-complex formation plays a role in the reactivity and substrate specificity
-
crystal structure of C273A/D145A, C273A/F329A and C273A/F329G double mutants at 2.25 A, 2.0 A and 1.9 A resolution, respectively; crystal structure of native histidase inactivated with L-cystein at 1.0 A and Y280F mutant histidase at 1.7 A
-
structure solved to 1.8 A resolution
-
wild-type and mutant
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
75
Achromobacter liquidum
-
15 min, stable for 30 min, without loss of activity
80
-
15 min, no loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
rapid decrease of activity in presence of mercaptoethanol or cysteine, 56% of initial activity after 1 d, 20% of initial activity after 2 d. In presence of DTT, the enzyme remains stable for several days
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
in the absence of L-cysteine enzyme is completely stable in an atmosphere of N2 and O2
-
34285
inactivation of the enzyme by L-cysteine requires presence of O2
-
34285
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, 50% loss of activity after 4 months
-
-20C, 0.05 M potassium phosphate buffer, pH 7.0, no significant loss of activity for 2 years
-
0-4C, in a tube containing a few drops of chloroform
-
0C, 24 h, pH 3.0 or pH 12.0, complete loss of activity
-
0C, 24 h, pH 7.0-10.0, enzyme retains full activity
-
0C, complete loss of activity within 1 week
-
2C, 0.1 M potassium phosphate, pH 7.2, 0.1 mM MnCl2 saturated with chloroform, stable for 9 months without loss of activity
-
37C, enzyme in solution: 50% loss of activity after 9.5 days, microencapsulated enzyme: 50% loss of activity after 15 days
-
4C, enzyme in solution: 27% loss of activity after 21 days, and 60% loss of activity after 77 days, microencapsulated enzyme: 5% loss of activity after 21 days, and less than 50% loss of activity after 77 days
-
5C, crystalline enzyme in 3.5 M ammonium sulfate, stable for 1 year
Achromobacter liquidum
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native and recombinant enzyme
-
recombinant histidase
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
expression in Escherichia coli as a His-tagged fusion protein
-
into the pT7-7 vector for expression in Escherichia coli BL21DE3 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
HAL2 is highly upregulated by T3
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A142D
-
3.4% of wild-type activity
A142G
-
93% of wild-type activity
C273A
-
20% of wild-type kcat
C273A/D145A
-
no activity, crystal structure
C273A/E414A
-
no activity
C273A/E414Q
-
0.06% of wild-type kcat
C273A/F329A
C273A/F329G
-
no activity, crystal structure
C273A/H83L
-
no activity
C273A/N195A
-
0.02% of wild-type kcat
C273A/Q277A
-
0.2% of wild-type kcat
C273A/R283I
-
0.9% of wild-type kcat
C273A/R283K
-
0.01% of wild-type kcat
C273A/Y280F
-
0.4% of wild-type kcat
C273A/Y53F
-
no activity
Cys273A
D145A
-
no activity
F329A
-
0.04% of wild-type activity
F329G
-
no activity
G141A
-
1.1% of wild-type activity
G144A
-
37% of wild-type activity
Y280F
-
0.9% of wild-type activity
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystalline enzyme is prepared with 24% recovery of activity
Achromobacter liquidum
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
a potentiometric sensor is made by immobilizing histidine ammonia-lyase on an ammonia gas-sensing electrode
synthesis
-
enzyme can be successfully microcapsulated within cellulose nitrate artificial cells
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