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 | 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 | Comment | Organism | Structure |
---|---|---|---|
4-phenyl-imidazole | 4-phenyl-imidazole coordinates transiently to the heme iron | Homo sapiens |
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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P14902 | - |
- |
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 | Comment | Organism |
---|---|---|
More | stucture-function analysis by spectrocopic methods, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
hIDO1 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
heme | - |
Homo sapiens |
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 |