Information on EC 1.22.1.1 - iodotyrosine deiodinase

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

EC NUMBER
COMMENTARY
1.22.1.1
-
RECOMMENDED NAME
GeneOntology No.
iodotyrosine deiodinase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-iodo-L-tyrosine + NADP+ + I- = 3,5-diiodo-L-tyrosine + NADPH + H+
show the reaction diagram
-
-
-
-
L-tyrosine + NADP+ + I- = 3-iodo-L-tyrosine + NADPH + H+
show the reaction diagram
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NADP+:L-tyrosine oxidoreductase (iodinating)
The enzyme activity has only been demonstrated in the direction of 3-deiodination. Present in a transmembrane flavoprotein. Requires FMN.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DEHAL1B
-
-
iodotyrosine dehalogenase 1
Q9DCX8
-
iodotyrosine deiodinase
Q9DCX8
-
IYD
Q9DCX8
-
lyd
Q9DCX8
gene name
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,5-diiodo-L-tyrosine + dithionite
3-iodo-L-tyrosine + ? + I-
show the reaction diagram
Q9DCX8
-
-
-
?
3,5-diiodo-L-tyrosine + dithionite
3-iodo-L-tyrosine + ? + I-
show the reaction diagram
-
solubilized enzyme preparations are active with dithionite, but not with NADPH. Particle-bound enzyme uses both dithionite and NADPH. At concentrations of substrate below 1 microM, 3,5-diiodo-L-tyrosine is more rapidly deiodinated than 3-iodo-L-tyrosine, which is reversed at concentrations greater than 5 microM
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
Q9DCX8
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
Q9DCX8
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
-
solubilized enzyme preparations are active with dithionite, but not with NADPH. Particle-bound enzyme uses both dithionite and NADPH. At concentrations of substrate below 1 microM, 3,5-diiodo-L-tyrosine is more rapidly deiodinated than 3-iodo-L-tyrosine, which is reversed at concentrations greater than 5 microM
-
-
?
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
Q6TA49
substrate 3-iodo-L-tyrosine is preferred over 3,5-diiodotyrosine
-
-
?
3-bromo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + Br-
show the reaction diagram
-
-
-
-
?
3-chloro-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + Cl-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
Q6TA49
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
Q9DCX8
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
while L-iodotyrosines are almost completely dehalogenated, D-iodotyrosines, alpha-methyl-DL-iodotyrosines and 3,5-diiodo-4-hydroxyphenyl-DL-lactic acid are poor substrates for the deiodinase. No substrates are 3,5-diiodo-4-hydroxyphenyl-alpha-guanidyl propionic acid, 3,5-diiodo-4-hydroxyphenyl propionic acid, 3,5-diiodotyramine, 3-iodo-5-nitro-L-tyrosine and 3-iodo-L-phenylalanine
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3,5-diiodo-L-tyrosine + NADPH + H+
3-iodo-L-tyrosine + NADP+ + I-
show the reaction diagram
Q9DCX8
-
-
-
?
3-iodo-L-tyrosine + NADPH + H+
L-tyrosine + NADP+ + I-
show the reaction diagram
Q9DCX8
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
-
flavin
-
presence of a neutral flavin radical during the reaction. Radical is stable and persists at 4C under aerobic conditions for many days
FMN
-
1 mol of FMN per mol of protein
FMN
-
enzyme is reduced in two successive 1-electron oxidation-reduction steps. The oxidation-reduction potential of the couple semiquinone/fully reduced enzyme is -0.412 V at pH 7 and 25C. The value for the oxidized/semiquinone couple is -0.190 V at pH 7 and 25C
FMN
Q9DCX8
-
FMNH2
Q9DCX8
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,2'-dipyridyl
-
-
3,5-diiodo-L-tyrosine
-
pronounced substrate inhibition above 5 microM
4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether
-
-
-
4'-hydroxy-2,2',4-tribromodiphenyl ether
-
-
-
4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl
-
-
4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether
-
-
-
4-hydroxy-2,3,3',4'-tetrabromodiphenyl ether
-
-
-
benzbromarone
-
-
N-ethylmaleimide
-
-
o-phenanthroline
-
-
phloxine B
-
-
Rose bengal
-
most potent inhibitor tested
triclosan
-
-
erythrosine B
-
-
additional information
-
among polychlorinated biphenyls and polybrominated diphenyl ethers without a hydroxyl group tested, including their methoxylated metabolites, none is inhibitory
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
maximal activity at 50 mM
FAD
-
up to 1.5fold stimulation
FAD
-
-
FMN
-
up to 1.5fold stimulation
FMN
-
-
additional information
-
enzyme activity increases at high ionic strength
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0011
3,5-diiodo-L-tyrosine
-
method NADPH oxidation, pH 7.4, 37C
0.0015
3,5-diiodo-L-tyrosine
-
method 125I release, pH 7.4, 37C
0.00202
3,5-diiodo-L-tyrosine
-
cosubstrate NADPH, pH 7.4, 25C
0.0025
3,5-diiodo-L-tyrosine
-
pH 7.4, 38C
0.0044
3,5-diiodo-L-tyrosine
-
cosubstrate dithionite, pH 7.4, 25C
0.019
3,5-diiodo-L-tyrosine
Q9DCX8
enzyme expressed in Pichia pastoris, pH not specified in the publication, temperature not specified in the publication
0.04
3,5-diiodo-L-tyrosine
Q9DCX8
enzyme expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
0.44
3,5-diiodo-L-tyrosine
Q9DCX8
mutant Y157F, expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
0.001
3-iodo-L-tyrosine
-
method NADPH oxidation, pH 7.4, 37C
0.0011
3-iodo-L-tyrosine
-
method 125I release, pH 7.4, 37C
0.004
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.0066
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.007
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.008
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.019
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.05
3-iodo-L-tyrosine
-
pH 7.4, 38C
0.027
NADPH
-
method 125I release, pH 7.4, 37C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.11
3,5-diiodo-L-tyrosine
-
cosubstrate dithionite, pH 7.4, 25C
0.12
3,5-diiodo-L-tyrosine
Q9DCX8
enzyme expressed in Pichia pastoris, pH not specified in the publication, temperature not specified in the publication
0.16
3,5-diiodo-L-tyrosine
Q9DCX8
enzyme expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
1.08
3,5-diiodo-L-tyrosine
Q9DCX8
mutant Y157F, expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
10
3,5-diiodo-L-tyrosine
-
pH 7.4, 38C
0.07
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.09
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.12
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.23
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
0.29
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
18
3-iodo-L-tyrosine
-
pH 7.4, 38C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.5
3,5-diiodo-L-tyrosine
Q9DCX8
mutant Y157F, expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
3597
3.83
3,5-diiodo-L-tyrosine
Q9DCX8
enzyme expressed in Escherichia coli and lacking the transmembrane domain, pH not specified in the publication, temperature not specified in the publication
3597
6
3,5-diiodo-L-tyrosine
Q9DCX8
enzyme expressed in Pichia pastoris, pH not specified in the publication, temperature not specified in the publication
3597
6
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
2332
8.5
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
2332
9.7
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
2332
41.7
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
2332
58.3
3-iodo-L-tyrosine
-
pH not specified in the publication, temperature not specified in the publication
2332
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.017
4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl
-
pH 7.4, 25C
0.011
benzbromarone
-
pH 7.4, 25C
0.0008
erythrosine B
-
pH 7.4, 25C
0.0008
phloxine B
-
pH 7.4, 25C
0.0002
Rose bengal
-
pH 7.4, 25C
0.019
triclosan
-
pH 7.4, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
stage 42, tail
6.1
-
stage 44, lower jaw
6.6
-
stage 46, lower jaw
9.2
-
stage 44, brain
17.9
-
stage 42, lower jaw
24.01
-
stage 44, lower jaw
28.4
-
stage 46, lower jaw
65.8
-
stage 42, brain
109
-
stage 42, brain
118.6
-
stage 44, tail
125
-
stage 46, brain
138.5
-
stage 42, tail
157.7
-
stage 44, brain
3100
-
pH 7.4, 25C
7800
-
pH 7.4, 38C
additional information
-
activity ranges from 0.0001 to 0.0003 microg/min/mg of tissue
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.3
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
during metamorphosis, DEHAL1 enzyme activity is higher on diiodotyrosine as compared to monoiodotyrosine. Using diiodotyrosine as a substrate, maximal activity is detected at stage 44 in the brain, while it is higher at stage 42 in the tail. With monoiodotyrosine as a substrate, highest activity is detected in the brain at stage 42
Manually annotated by BRENDA team
-
tadpole tail fin. During metamorphosis, DEHAL1 enzyme activity is higher on diiodotyrosine as compared to monoiodotyrosine. Using diiodotyrosine as a substrate, maximal activity is detected at stage 44 in the brain, while it is higher at stage 42 in the tail (138.5 U/mg protein). With monoiodotyrosine as a substrate, highest activity is detected in the brain at stage 42
Manually annotated by BRENDA team
-
ventricular lining of the fourth ventricle
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
transmembrane protein, partly exposed to cell surface, protein accumulates at the apical pole of thyrocytes
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42000
-
gel filtration
704368
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 30000, SDS-PAGE
?
Q9DCX8
x * 30000, SDS-PAGE
?
-
x * 32800, SDS-PAGE and calculated
?
-
x * 33000, SDS-PAGE and calculated
?
Q6PHW0
x * 33000, SDS-PAGE and calculated
dimer
-
2 * 22300, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
Q6PHW0
putative signal peptide with a possible cleavage site between Ala23 and Asp24
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging dop vapor diffusion method, using 0.2 M ammonium acetate, 0.1 M BisTris (pH 6.5), and 45% v/v 2-methyl-2,4-pentanediol; structure of a truncated derivative lacking the membrane domain, residues 2-33, at its N-terminal, and its complex with substrate monoiodotyrosine. In the absence of substrate, the active site appears very accessible to solvent due to a lack of detectable structure in two surrounding regions of the polypeptide. In the presence of substrate, an active site lid comprised of a helix and loop is detected from the diffraction data. This lid effectively sequesters the substrate-flavin complex from solvent
Q9DCX8
structures of soluble enzyme lacking codons for amino acids 2-33 and two co-crystals containing substrates, mono- and diiodotyrosine, alternatively, at resolutions of 2.0 A, 2.45 A, and 2.6 A, respectively. Substrate coordination induces formation of an additional helix and coil that act as an active site lid to shield the resulting substrateflavin complex from solvent. This complex is stabilized by aromatic stacking and extensive hydrogen bonding between the substrate and flavin. The carbon-iodine bond of the substrate is positioned directly over the C-4a/N-5 region of the flavin to promote electron transfer
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15 to -20C in 10 mM phosphate buffer, stable for months
-
0 to 4C in 10 mM phosphate buffer, stable for weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purification of stable aporptoein
-
HiTrap column chromatography
Q9DCX8
solubilization by 0.1% CHAPS
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in HEK-293T cell
-
expressed in Sf9 insect cells and in Escherichia coli
Q9DCX8
expression in HEK-293 cell
-
expression of a derivative lacking codons for amino acids 233 to gain a soluble protein
-
transfection of HEK-293 cells results in active protein, but not of CHO cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
study on enzyme expression in thyroid pathology. The highest DEHAL1 mRNA levels are found in Graves' disease thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurrs in papillary thyroid carcinomas and anaplastic thyroid carcinomas. DEHAL1 protein is overexpressed in toxic thyroid nodules and Graves' disease thyroids with predominant apical staining in all samples. A weaker and patchy staining pattern is found in benign cold thyroid nodules and normal thyroids. In differentiated thyroid cancers such as follicular thyroid carcinomas and papillary thyroid carcinomas, a diffuse cytoplasmic DEHAL1 expression is found. In partially differentiated thyroid cancers and anaplastic thyroid carcinomas, DEHAL1 expression is faint or absent
-
DEHAL12 is upregulated by cAMP
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E153Q
Q9DCX8
the mutant exhibits no measurable binding affinity for 3-chloro-L-tyrosine
E153Q
Q9DCX8
mutation reduces the deiodinase activity to an undetectable level. Mutant exhibits no measurable binding affinity for the substrate
K178Q
Q9DCX8
upon expression in Escherichia coli, inactive and insoluble
Y157F
Q9DCX8
the mutation weakens the binding of 3-chloro-L-tyrosine by 20fold
Y157F
Q9DCX8
lack of the phenolic -OH of Y157F increases the kcat and KM values for deiodination by more than sevenfold and decreases the kcat/KM value more modestly by less than 40%
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
activation of purified enzyme by dithionite, methyl viologen, or ferredoxin, but not by photo-reduced FMN or by reducing agents having more positive oxidation-reduction potentials than the ferredoxin-NADP system
-
apoprotein binds FMN with an almost complete restoration of enzymatic activity. It can also bind FAD with partial restoration of activity, but does not bind riboflavin
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
study on enzyme expression in thyroid pathology. The highest DEHAL1 mRNA levels are found in Graves' disease thyroids, while downregulation of DEHAL1 and DEHAL1B mRNA occurrs in papillary thyroid carcinomas and anaplastic thyroid carcinomas. DEHAL1 protein is overexpressed in toxic thyroid nodules and Graves' disease thyroids with predominant apical staining in all samples. A weaker and patchy staining pattern is found in benign cold thyroid nodules and normal thyroids. In differentiated thyroid cancers such as follicular thyroid carcinomas and papillary thyroid carcinomas, a diffuse cytoplasmic DEHAL1 expression is found. In partially differentiated thyroid cancers and anaplastic thyroid carcinomas, DEHAL1 expression is faint or absent
synthesis
Q9DCX8
high expression of a truncated derivative lacking the membrane domain, residues 2-33, at its N-terminal is observed in Sf9 cells, whereas expression in Pichia pastoris remains low despite codon optimization. The desired expression in Escherichia coli can be achieved after replacing the two conserved Cys residues of the deiodinase with Ala and fusing the resulting protein to thioredoxin. This construct provides abundant enzyme for crystallography and mutagenesis