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Information on EC 4.3.1.3 - histidine ammonia-lyase and Organism(s) Pseudomonas putida and UniProt Accession P21310
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4.3.1.3 histidine ammonia-lyaseIUBMB Comments
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 . This unique cofactor is formed autocatalytically by cyclization and dehydration of the three amino-acid residues alanine, serine and glycine . This enzyme catalyses the first step in the degradation of histidine and the product, urocanic acid, is further metabolized to glutamate [2,3].
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The taxonomic range for the selected organisms is: Pseudomonas putida
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
hal, histidase, histidine ammonia-lyase, histidine ammonia lyase, histidinase, l-histidase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ammonia-lyase, histidine
-
-
-
-
HAL
histidase
-
-
-
-
histidase, Hut
-
-
-
-
histidinase
-
-
-
-
histidine alpha-deaminase
-
-
-
-
histidine deaminase
-
-
-
-
L-HAL
-
-
-
-
L-histidase
-
-
-
-
L-histidine NH3-lyase
-
-
-
-
HAL
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
9013-75-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-histidine methyl ester
urocanate methyl ester
-
cloned enzyme
cloned enzyme
?
additional information
?
-
-
Ser-143 is an essential active site residue in the enzyme
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
Ser-143 is an essential active site residue in the enzyme
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-amino-2-imidazol-4'-ylethylphosphonic acid
-
reversible, competitive, 1 mM: complete inhibition
8-methoxypsoralen
-
noncompetitive. Irradiation of 8-methoxypsoralen with broadband UVA and broadband UVA/UVB results in uncompetitive inhibition due to psoralen-oxidized photoproducts
L-cysteine
10 mM, complete inactivation at pH higher than 10 in the presence of O2
bisulfite
-
10 mM, 95% loss of activity after 90 min, 0.1 mM 1-amino-2-imidazol-4'-ylethylphosphoric acid protects
L-cysteine
-
10 mM, complete inactivation after 3 h under aerobic conditions
L-cysteine
-
50 mM, complete inaction at basic pH in the presence of O2 is due to a covalent modification of the enzyme
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
0.018
(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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
-10 - 60
-
-10°C: pH 9.2, assay mixture containing 21% dimethylsulfoxide remains liquid, activity is 5,8% of the activity at 30°C, 60°C: 20% of maximal activity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
a 3,5-dihydro-5-methylidene-4H-imidazol-4-one electrophilic moiety is post-translationally and autocatalytically generated in homotetrameric histidine ammonia-lyase containing the tripeptide Ala-Ser-Gly in a suitably positioned loop. Dehydration, rather than dehydrogenation by molecular oxygen, is the reaction that gives rise to the mature MIO ring system. Water molecules play a highly relevant role in the reaction mechanism. The backbone cyclization resulting from the nucleophilic attack of the Gly amide lone pair on the pi orbital of the Ala carbonyl precedes side-chain dehydration of the central serine
additional information
-
a 3,5-dihydro-5-methylidene-4H-imidazol-4-one electrophilic moiety is post-translationally and autocatalytically generated in homotetrameric histidine ammonia-lyase containing the tripeptide Ala-Ser-Gly in a suitably positioned loop. Dehydration, rather than dehydrogenation by molecular oxygen, is the reaction that gives rise to the mature MIO ring system. Water molecules play a highly relevant role in the reaction mechanism. The backbone cyclization resulting from the nucleophilic attack of the Gly amide lone pair on the pi orbital of the Ala carbonyl precedes side-chain dehydration of the central serine
additional information
-
the peptide at the active center of the enzyme is considered to be posttranslationally dehydrated to form an electrophilic 4-methylidene-imidazole-one group
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C273A/F329A
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Consevage, M.W.; Porter, R.D.; Phillips, A.T.
Cloning and expression in Escherichia coli of histidine utilization genes from Pseudomonas putida
J. Bacteriol.
162
138-146
1985
Pseudomonas putida
Rechler, M.M.; Tabor, H.
Histidine ammonia-lyase (Pseudomonas)
Methods Enzymol.
17B
63-69
1971
Pseudomonas sp., Pseudomonas aeruginosa, Pseudomonas putida
-
Hassall, H.
Use of L-histidine ammonia-lyase for the determination of L-histidine
Methods Enzymol.
17B
895-897
1971
Homo sapiens, Pseudomonas sp., Pseudomonas putida
-
Hug, D.H.; Hunter, J.K.
Effect of temperature on histidine ammonia-lyase from a psychrophile, Pseudomonas putida
J. Bacteriol.
119
92-97
1974
Pseudomonas putida, Rattus norvegicus, Pseudomonas putida A.3.12
Shibatani, T.; Kakimoto, T.; Chibata, I.
Crystalline L-histidine ammonia-lyase of Achromobacter liquidum. Crystallization and enzymic properties
Eur. J. Biochem.
55
263-269
1975
Achromobacter liquidum, Bacillus cereus, Bacillus subtilis, Comamonas testosteroni, Helianthus sp., Mycobacterium avium, Pseudomonas sp., Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas fluorescens, Rattus norvegicus, Salmonella enterica subsp. enterica serovar Typhimurium, Spinacia oleracea, Vibrio cholerae serotype O1, Achromobacter liquidum IAM 1667
Hernandez, D.; Phillips, A.T.
Purification and Characterization of Pseudomonas putida histidine ammonia-lyase expressed in Escherichia coli
Protein Expr. Purif.
4
473-478
1993
Pseudomonas sp., Pseudomonas putida, Pseudomonas putida PRS1
Hernandez, D.; Phillips, A.T.; Zon, J.
1-amino-2-imidazol-4 -ylethylphosphonic acid is a potent reversible inhibitor of Pseudomonas putida histidine ammonia-lyase
Biochem. Mol. Biol. Int.
32
189-194
1994
Pseudomonas putida
Hernandez, D.; Phillips, A.T.
Ser-143 is an essential active site residue in histidine ammonia-lyase of Pseudomonas putida
Biochem. Biophys. Res. Commun.
201
1433-1438
1994
Pseudomonas putida
Weber, K.; Retey, J.
On the nature of the irreversible inhibition of histidine ammonia lyase by cysteine and dioxygen
Bioorg. Med. Chem.
4
1001-1006
1996
Pseudomonas putida
Schwede, T.F.; Baedeker, M.; Langer, M.; Retey, J.; Schulz, G.E.
Homogenization and crystallization of histidine ammonia-lyase by exchange of a surface cysteine residue
Protein Eng.
12
151-153
1999
Pseudomonas putida
Schwede, T.F.; Retey, J.; Schulz, G.E.
Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile
Biochemistry
38
5355-5361
1999
Pseudomonas putida (P21310), Pseudomonas putida
Rother, D.; Poppe, L.; Viergutz, S.; Langer, B.; Retey, J.
Characterization of the active site of histidine ammonia-lyase from Pseudomonas putida
Eur. J. Biochem.
268
6011-6019
2001
Pseudomonas putida (P21310), Pseudomonas putida
Merkel, D.; Retey, J.
Further insight into the mechanism of the irreversible inhibition of histidine ammonia-lyase by L-cysteine and dioxygen
Helv. Chim. Acta
83
1151-1160
2000
Pseudomonas putida
-
Galpin, J.D.; Ellis, B.E.; Tanner, M.E.
The Inactivation of Histidine Ammonia-Lyase by L-Cysteine and Oxygen: Modification of the Electrophilic Center
J. Am. Chem. Soc.
121
10840-10841
1999
Pseudomonas putida
-
Baedeker, M.; Schulz, G.E.
Autocatalytic peptide cyclization during chain folding of histidine ammonia-lyase
Structure
10
61-67
2002
Pseudomonas putida (P21310)
Asano, Y.; Kato, Y.; Levy, C.; Baker, P.; Rice, D.
Structure and Function of Amino Acid Ammonia-lyases
Biocatal. Biotransform.
22
131-138
2004
Pseudomonas putida
-
Katona, A.; Tosa, M.I.; Paizs, C.; Retey, J.
Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates
Chem. Biodivers.
3
502-508
2006
Pseudomonas putida
Seff, A.L.; Pilbak, S.; Silaghi-Dumitrescu, I.; Poppe, L.
Computational investigation of the histidine ammonia-lyase reaction: a modified loop conformation and the role of the zinc(II) ion
J. Mol. Model.
17
1551-1563
2011
Pseudomonas putida
Reilly, J.T.; Troester, K.A.; Tyner, T.T.; Vitale, D.A.; Risher, T.R.
Inhibition of histidine ammonia lyase by 8-methoxypsoralen and psoralen-oxidized photoproducts
Photochem. Photobiol.
86
1272-1277
2010
Pseudomonas putida
Sanchez-Murcia, P.A.; Bueren-Calabuig, J.A.; Camacho-Artacho, M.; Cortes-Cabrera, A.; Gago, F.
Stepwise simulation of 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) biogenesis in histidine ammonia-lyase
Biochemistry
55
5854-5864
2016
Pseudomonas putida (P21310), Pseudomonas putida
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