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Literature summary for 1.13.11.52 extracted from

  • Capece, L.; Lewis-Ballester, A.; Marti, M.A.; Estrin, D.A.; Yeh, S.R.
    Molecular basis for the substrate stereoselectivity in tryptophan dioxygenase (2011), Biochemistry, 50, 10910-10918.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.13.11.52

Protein Variants

Protein Variants Comment Organism
T254A ternary complex molecular simulations. The mutation causes the opening of the loop 250-260 to loop 117-130, leading to a more dynamic and open distal pocket, accounting for the much lower substrate affinity (i.e. higher Km). On the other hand, the simulation data of the ferryl/L-indole 2,3-epoxide intermediate indicate that the T254A mutation also results in the opening of the loop 250-260 to loop 117-130. It leads to local reorganization of the H-bonding interactions surrounding the NH3+ group of the substrate, resulting in an open conformation, in which the H-bond between the NH3+ and the epoxide is temporarily lost Xanthomonas campestris
T342A site-directed mutagenesis, the mutation only slightly perturbs the global structural properties of the enzyme, but it totally abolishes the substrate stereoselectivity, substrate-free spectrum Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.119
-
 L-tryptophan pH 7.0, 25°C, mutant T342A Homo sapiens
0.12
-
 L-tryptophan pH 7.0, 25°C, wild-type enzyme Homo sapiens
0.159
-
 D-tryptophan pH 7.0, 25°C, mutant T342A Homo sapiens
0.26
-
 D-tryptophan pH 7.0, 25°C, wild-type enzyme Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Fe2+ heme-containing enzyme Homo sapiens
Fe2+ heme-containing enzyme Xanthomonas campestris

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-tryptophan + O2 Xanthomonas campestris
-
 N-formyl-L-kynurenine
-
 ?
L-tryptophan + O2 Homo sapiens human TDO displays a major specificity towards L-Trp, structural role of T342 in controlling the substrate stereoselectivity of the enzyme N-formyl-L-kynurenine
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Xanthomonas campestris
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-tryptophan + O2 low activity Homo sapiens N-formyl-D-kynurenine
-
 ?
L-tryptophan + O2
-
 Xanthomonas campestris N-formyl-L-kynurenine
-
 ?
L-tryptophan + O2 human TDO displays a major specificity towards L-Trp, structural role of T342 in controlling the substrate stereoselectivity of the enzyme Homo sapiens N-formyl-L-kynurenine
-
 ?
L-tryptophan + O2 highly preferred substrate, T342 plays a pivotal role in controlling the substrate stereoselectivity of hTDO Homo sapiens N-formyl-L-kynurenine
-
 ?

Synonyms

Synonyms Comment Organism
TDO
-
 Homo sapiens
TDO
-
 Xanthomonas campestris
tryptophan dioxygenase
-
 Homo sapiens
tryptophan dioxygenase
-
 Xanthomonas campestris

Temperature Optimum [°C]

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

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.082
-
 D-tryptophan pH 7.0, 25°C, mutant T342A Homo sapiens
0.101
-
 L-tryptophan pH 7.0, 25°C, mutant T342A Homo sapiens
0.2
-
 D-tryptophan pH 7.0, 25°C, wild-type enzyme Homo sapiens
2.24
-
 L-tryptophan pH 7.0, 25°C, wild-type enzyme Homo sapiens

pH Optimum

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

Cofactor

Cofactor Comment Organism Structure
heme
-
 Homo sapiens
heme
-
 Xanthomonas campestris

General Information

General Information Comment Organism
additional information molecular dynamics simulation studies, overview. Structural role of T342 in controlling the substrate stereoselectivity of the enzyme Homo sapiens
additional information Xanthomonas campestris TDO shows an H-bond between T254 and the ammonium group of the substrate is present in the L-Trp-bound enzyme, but not in the D-Trp bound enzyme, molecular dynamics simulation studies. T254 controls the substrate stereoselectivity of the enzyme by modulating the H-bonding interaction between the NH3-group and epoxide oxygen of the ferryl/indole 2,3-epoxide intermediate of the enzyme, and regulating the dynamics of two active site loops, loop250-260 and loop117-130, critical for substrate-binding, O2 and L-trp both are bound in the active site Xanthomonas campestris
physiological function the enzyme is responsible for L-Trp processing that ultimately leads to the biosynthesis of NAD+ and NADP+ Homo sapiens