Literature summary for 1.21.1.1 extracted from

Hu, J.; Chuenchor, W.; Rokita, S.E.
A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate (2015), J. Biol. Chem., 290, 590-600.

Cloned(Commentary)

Cloned (Comment)	Organism
gene DEHAL1, recombinant expression of N-terminally SUMO-tagged enzyme in Escherichia coli strain Rosetta 2(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme in complex with substrate 3-iodo-L-tyrosine, method optimization, hanging drop diffusion method, mixing of 0.001 ml of 12 mg/ml protein in 50mM sodium phosphate, pH 7.4, 100 mM NaCl, 1 mM DTT, and 10% glycerol with 0.001 ml of precipitant solution containing 0.05 M ammonium sulfate, 50 mM BisTris, pH 6.5, and 25% pentaerythritol ethoxylate, 2 days, 20°C. To generate co-crystals the enzyme is treated with 1.5 mM 3-iodo-L-tyrosine overnight and then subjected to the same hanging drop procedure using a well solution of 0.15 M sodium acetate, 85mM Tris-HCl, pH 8.5, 25.5% w/v PEG 4000, and 15% glycerol at 20 °C, 24 h, X-ray diffraction structure determination and analysis at 2.45-2.65 A resolution, molecular replacement	Homo sapiens

Crystallization (Comment)

Organism

purified enzyme in complex with substrate 3-iodo-L-tyrosine, method optimization, hanging drop diffusion method, mixing of 0.001 ml of 12 mg/ml protein in 50mM sodium phosphate, pH 7.4, 100 mM NaCl, 1 mM DTT, and 10% glycerol with 0.001 ml of precipitant solution containing 0.05 M ammonium sulfate, 50 mM BisTris, pH 6.5, and 25% pentaerythritol ethoxylate, 2 days, 20°C. To generate co-crystals the enzyme is treated with 1.5 mM 3-iodo-L-tyrosine overnight and then subjected to the same hanging drop procedure using a well solution of 0.15 M sodium acetate, 85mM Tris-HCl, pH 8.5, 25.5% w/v PEG 4000, and 15% glycerol at 20 °C, 24 h, X-ray diffraction structure determination and analysis at 2.45-2.65 A resolution, molecular replacement

Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	Michaelis-Menten steady-state kinetics. Dissociation constants for different substrate analogues, overview	Homo sapiens
0.031	-	3-iodo-L-tyrosine	pH 7.6, temperature not specified in the publication, recombinant enzyme	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
membrane	transmembrane enzyme	Homo sapiens	16020	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
30000	-	two identical subunits of human IYD form an alphabeta fold, 2 * 30000, recombinant enzyme, SDS-PAGE	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-tyrosine + 2 NADP+ + 2 iodide	Homo sapiens	-	3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q6PHW0	gene DEHAL1	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant SUMO-tagged enzyme from Escherichia coli strain Rosetta 2(DE3) by nickel affinity chromatography, tag removal, and gel filtration	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
thyroid gland	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
3-iodo-L-tyrosine + NADPH + H+	-	Homo sapiens	L-tyrosine + NADP+ + iodide	-	r
L-tyrosine + 2 NADP+ + 2 iodide	-	Homo sapiens	3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+	-	r
L-tyrosine + 2 NADP+ + 2 iodide	-	Homo sapiens	3,5-diiodo-L-tyrosine + 2 NADPH + 2 H+	stepwise single electron transfer involving FMN, ferredoxin, and NADPH, overview. Ability of the substrate to provide multiple interactions with the isoalloxazine system ofFMN that are usually provided by protein side chains. Ligand binding acts to template the active site geometry and significantly stabilize the one-electron-reduced semiquinone form of FMN	r
L-tyrosine + NADP+ + iodide	-	Homo sapiens	3-iodo-L-tyrosine + NADPH + H+	-	r
additional information	a synergy between substrate selectivity and catalytic activity is created by the enzyme. No activity with the substrate analog 3-fluoro-L-tyrosine	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
heterodimer	two identical subunits of human IYD form an alphabeta fold, 2 * 30000, recombinant enzyme, SDS-PAGE	Homo sapiens
More	the enzyme contains three domains: an N-terminal transmembrane region, an intermediate domain, and a catalytic domain	Homo sapiens

Synonyms

Synonyms	Comment	Organism
IYD	-	Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism	Structure
0.208	-	3-iodo-L-tyrosine	pH 7.6, temperature not specified in the publication, recombinant enzyme	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.6	-	assay at	Homo sapiens

pH Range

pH Minimum	pH Maximum	Comment	Organism
6	9	pH dependence of IYD binding and turnover, tightest binding was measured near a neutral pH of 7.67.7	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
FMN	FMN binds non-covalently at the dimer interface established by a helix from each of the two identical subunits involving residues Ser102 and Ser128. Iodotyrosine deiodinase utilizes FMN to maintain iodide homeostasis by reductive deiodination of iodotyrosine. In the absence of an active site ligand, only the oxidized and two-electron-reduced forms of FMN are detected	Homo sapiens

General Information

General Information	Comment	Organism
evolution	domain swaps at each N and C terminus consistent with the nitro-FMN reductase superfamily	Homo sapiens
additional information	a synergy between substrate selectivity and catalytic activity is created by the enzyme, active site and cofactor and substrate binding structures, overview	Homo sapiens
physiological function	iodotyrosine deiodinase utilizes FMN to maintain iodide homeostasis by reductive deiodination of iodotyrosine	Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism	Structure
6.72	-	3-iodo-L-tyrosine	pH 7.6, temperature not specified in the publication, recombinant enzyme	Homo sapiens