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Literature summary for 1.8.1.6 extracted from

  • Pader, I.; Sengupta, R.; Cebula, M.; Xu, J.; Lundberg, J.O.; Holmgren, A.; Johansson, K.; Arner, E.S.
    Thioredoxin-related protein of 14 kDa is an efficient L-cystine reductase and S-denitrosylase (2014), Proc. Natl. Acad. Sci. USA, 111, 6964-6969 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) Homo sapiens

Protein Variants

Protein Variants Comment Organism
C43S/C46S site-directed mutagenesis, inactive mutant Homo sapiens
C46S site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme Homo sapiens
additional information knockdown and overexpression of TRP14 affect total L-cystine reduction capacity and S-nitrosoprotein levels in crude HEK-293 cell lysate Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information Michaelis-Menten kinetics Homo sapiens
0.0008
-
L-cystine pH 7.5, 22°C, wild-type enzyme TRP14 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Homo sapiens 5829
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-cystine + NADH + H+ Homo sapiens
-
2 L-cysteine + NAD+
-
?
additional information Homo sapiens enzyme TRP14 not being able to reduce any classical protein disulfide substrates of thioredoxin 1, Trx1. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9BRA2
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3) Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
A-431 cell high enzyme expression level Homo sapiens
-
HEK-293 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-cystine + NADH + H+
-
Homo sapiens 2 L-cysteine + NAD+
-
?
additional information enzyme TRP14 not being able to reduce any classical protein disulfide substrates of thioredoxin 1, Trx1. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase Homo sapiens ?
-
?
additional information enzyme TRP14 has S-denitrosylase activity performing GSNO reduction with realease of NO, it is also active with L-CysSNO Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
L-cystine reductase
-
Homo sapiens
thioredoxin domain containing 17
-
Homo sapiens
thioredoxin-like 5
-
Homo sapiens
TRP14
-
Homo sapiens
TXNDC17
-
Homo sapiens
TXNL5
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
22
-
assay at room temperature Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
30.3
-
L-cystine pH 7.5, 22°C, wild-type enzyme TRP14 Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADH
-
Homo sapiens

General Information

General Information Comment Organism
evolution the enzyme belongs to the member of the thioredoxin (Trx)-fold protein family. The enzyme lacks activity with classical thioredoxin, Trx1, substrates. Human enzyme TRP14 has high enzymatic activity in reduction of L-cystine, where the catalytic efficiency coupled to Trx reductase 1 (TrxR1) using NADPH is fivefold higher than the activity of enzyme Trx1 alone. Trx1-mediated L-cystine reduction is inefficient in the presence of other preferred Trx1 substrates whereas, conversely, TRP14 seems to be a more dedicated L-cystine reductase Homo sapiens
additional information the disulfide/dithiol motif formed by Cys43 and Cys46 is the active site of TRP14 Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
37875
-
L-cystine pH 7.5, 22°C, wild-type enzyme TRP14 Homo sapiens