Literature summary for 1.13.11.52 extracted from

Kolawole, A.O.; Hixon, B.P.; Dameron, L.S.; Chrisman, I.M.; Smirnov, V.V.
Catalytic activity of human indoleamine 2,3-dioxygenase (hIDO1) at low oxygen (2015), Arch. Biochem. Biophys., 570, 47-57 .

Search for more literature for 1.13.11.52

Cloned(Commentary)

Cloned (Comment)	Organism
gene IDO1, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Star (DE3), real-time PCR enzyme expression analysis	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
1-methyl-L-tryptophan	competitive versus L-Trp and noncompetitive versus O2. When 1-Me-L-Trp is the only indoleamine in the reaction mixture, it is a very slow substrate for hIDO1	Homo sapiens
norharmane	NHM, noncompetitive versus L-Trp and competitive versus O2	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	stopped-flow and Michaelis-Menten steady-state kinetic measurements, kinetic model for catalytic dioxygenation of L-Trp by hIDO1, detailed overview. At low O2, the reversibility of the first step is essential for accurate reproduction of experimental O2 kcat/KM ratios	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Fe2+	ferric heme	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
D-tryptophan + O2	Homo sapiens	-	N-formyl-D-kynurenine	-	?
L-tryptophan + O2	Homo sapiens	-	N-formyl-L-kynurenine	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P14902	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21 Star (DE3) by two steps of nickel affinity chromatography and dialysis	Homo sapiens

Reaction

Reaction	Comment	Organism	Reaction ID
L-tryptophan + O2 = N-formyl-L-kynurenine	steady-state kinetic catalytic mechanism of hIDO1	Homo sapiens	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
D-tryptophan + O2	-	Homo sapiens	N-formyl-D-kynurenine	-	?
L-tryptophan + O2	-	Homo sapiens	N-formyl-L-kynurenine	-	?
additional information	using a cytochrome b5-based activating system, the initial rates of O2 decay with a Clark-type oxygen electrode at physiologically-relevant levels of both substrates are measured. Kinetics are also studied in the presence of two inhibitory substrate analogues: 1-methyl L-tryptophan and norharmane. Quantitative analysis supports a steady-state rather than a rapid equilibrium kinetic mechanism, where the rates of individual pathways, leading to a ternary complex, are significantly different, and the overall rate of catalysis depends on contributions of both routes. One path, where O2 binds to ferrous hIDO1 first, is faster than the second route, which starts with the binding of L-Trp. L-Trp complexation with free ferrous hIDO1 is more rapid than that of O2. As the level of L-Trp increases, the slower route becomes a significant contributor to the overall rate, resulting in observed substrate inhibition. When 1-Me-L-Trp is the only indoleamine in the reaction mixture, it is a very slow substrate for hIDO1	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
hIDO1	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	Homo sapiens

pH Optimum

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

Cofactor

Cofactor	Comment	Organism	Structure
heme	ferric heme	Homo sapiens

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.0052	-	1-methyl-L-tryptophan	pH 7.0, 25°C, versus L-tryptophan and O2	Homo sapiens
0.012	-	norharmane	pH 7.0, 25°C, versus O2	Homo sapiens
0.03	-	norharmane	pH 7.0, 25°C, versus L-tryptophan	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	the enzyme is cytokine-inducible	up

General Information

General Information	Comment	Organism
physiological function	the cytokine-inducible extrahepatic human indoleamine 2,3-dioxygenase (hIDO1) catalyzes the first step of the kynurenine pathway. Immunosuppressive activity of hIDO1 in tumor cells weakens host T-cell immunity, contributing to the progression of cancer	Homo sapiens

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Release 2023.1 (January 2023)