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Literature summary for 1.13.11.52 extracted from

  • Nienhaus, K.; Nickel, E.; Nienhaus, G.U.
    Substrate binding in human indoleamine 2,3-dioxygenase 1 a spectroscopic analysis (2017), Biochim. Biophys. Acta, 1865, 453-463 .
    View publication on PubMed
Search for more literature for 1.13.11.52

Application

Application Comment Organism
drug development increased levels of hIDO1 expression in tumor cells correlate with a poor prognosis for surviving several cancer types. hIDO1 is a drug target for cancer therapy, design of de novo inhibitors selective for hIDO1. Homo sapiens

Protein Variants

Protein Variants Comment Organism
A264G site-directed mutagenesis, mutation of a loop residues that connects the hIDO domains Homo sapiens
G261A site-directed mutagenesis, mutation of a loop residues that connects the hIDO domains Homo sapiens
G261V site-directed mutagenesis, mutation of a loop residues that connects the hIDO domains Homo sapiens
R213E site-directed mutagenesis, mutation of an active site residue Homo sapiens
R231A site-directed mutagenesis, mutation of an active site residue involved in substrate binding Homo sapiens
S167H site-directed mutagenesis, mutation of an active site residue Homo sapiens
S167L site-directed mutagenesis, mutation of an active site residue Homo sapiens
S263A site-directed mutagenesis, mutation of a loop residues that connects the hIDO domains Homo sapiens
T379A site-directed mutagenesis, mutation of an active site residue involved in substrate binding. In the T379A variant, Arg231 may be able to capture L-Trp close to the heme, but the active site cannot be closedwithout Thr379 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
4-phenyl-imidazole 4-phenyl-imidazole coordinates transiently to the heme iron Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information bimolecular CO association rate coefficients, 22°C 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
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-tryptophan + O2
-
 Homo sapiens N-formyl-D-kynurenine
-
 ?
D-tryptophan + O2 D-Trp is a substrate of hIDO1 but has very low affinity Homo sapiens N-formyl-D-kynurenine
-
 ?
L-tryptophan + O2
-
 Homo sapiens N-formyl-L-kynurenine
-
 ?
additional information the heme enzyme catalyzes the oxidative cleavage of the Ltryptophan indole ring Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
More stucture-function analysis by spectrocopic methods, overview Homo sapiens

Synonyms

Synonyms Comment Organism
hIDO1
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
heme
-
 Homo sapiens

General Information

General Information Comment Organism
additional information important amino acid residues that stabilize the substrate in the active site: a cluster of small side chain residues at positions 260-265 ensures structural flexibility of the binding site. Thr379 and Arg231 are key residues acting in concert to bind the substrate. Thr379 is the final residue of a disordered loop, the neighboring Gly380 is 20 A away from the heme iron. Residues Ser167, Phe226, Phe227, and Arg231 may play critical roles. Stucture-function analysis by spectrocopic methods, overview. The hIDO1 distal heme pocket is in part lined by a sequence of residues with small side chains (residues 260-265: AGGSAG) rendering structural flexibility to the active site, which may be required to accommodate the substrate Homo sapiens