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1.17.4.2: ribonucleoside-triphosphate reductase (thioredoxin)

This is an abbreviated version!
For detailed information about ribonucleoside-triphosphate reductase (thioredoxin), go to the full flat file.

Word Map on EC 1.17.4.2

Reaction

2'-deoxyribonucleoside 5'-triphosphate
+
thioredoxin disulfide
 +
H2O
=
ribonucleoside 5'-triphosphate
 +
thioredoxin

Synonyms

2'-deoxyribonucleoside-triphosphate:oxidized-thioredoxin 2'-oxidoreductase, adenosylcobalamin-dependent ribonucleoside-triphosphate reductase, class Ib ribonucleotide reductase, class Ib RNR, class II ribonucleotide reductase, class II RNR, class III ribonucleotide reductase, class III RNR, More, nrdD, nucleoside triphosphate reductase, ribonucleoside triphosphate reductase, ribonucleotide diphosphate reductase, ribonucleotide reductase, RNR, RNR class Ia, RNR2, RTPR

ECTree

     1 Oxidoreductases
         1.17 Acting on CH or CH2 groups
             1.17.4 With a disulfide as acceptor
                1.17.4.2 ribonucleoside-triphosphate reductase (thioredoxin)

Inhibitors

Inhibitors on EC 1.17.4.2 - ribonucleoside-triphosphate reductase (thioredoxin)

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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2',2'-difluoro-2'-deoxycytidine 5'-triphosphate
2'-chloro-2'-deoxy-UTP
-
-
2'-deoxyadenosylcobalamin
-
-
3,3',4,4',5,5'-hexahydroxy-trans-stilbene
-
i.e. M8, a resveratrol analogue, inhibits the enzyme and causes an imbalance of intracellular dNTP pools, the dATP pool is eliminated, while the dCTP and dTTP pools are enlarged. M8 leads to complete growth inhibition of HT-29 cells at 0.015 mM within 7 days, overview
3-aminopyridine-2-carboxaldehyde thiosemicarbazone
-
i.e.3-AP or triapine, in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloprol, phase I study, detailed overview, the inhibitor inhibits the M2 subunit, and depletes intracellular deoxyribonculeotide pools, especially dATP
3-aminopyridine-2-carboxaldehyde-thiosemicarbazone
-
i.e. 3-AP, phase I study in combination with high dose cytarabine in patients with advanced myeloid leukemia, resulting in enhanced cytarabine cytotoxicity with possible methemoglobinemia, overview
3-isoadenosylcobalamin
-
-
adenosylcobalamin
-
-
caracemide
chlorambucil
cisplatin
cob(II)alamin
-
-
cyanocobalamin
-
-
gallic acid
-
inhibition of enzyme activity and induction of dose-dependent apoptosis and attenuated progression from G0/G1 to S phase of cells cycle. Highly synergistic effects of simultaneous treatment of cells with gallic acid and enzyme inhibitor N',3,4,5-tetrahydroxybenzenecarboximidamide
gemcitabine
Hydroxyurea
IRBIT
-
IRBIT is a conserved metazoan protein implicated in diverse functions. IRBIT consists of a putative enzymatic domain that has similarity to S-adenosylhomocysteine hydrolase and an essential N-terminal domain of 104 amino acids. It forms a dATP-dependent complex with ribonucleotide reductase, which stabilizes dATP in the activity site of ribonucleotide reductase and thus inhibits the enzyme. Formation of the ribonucleotide reductase-IRBIT complex is regulated through phosphorylation of IRBIT, and ablation of IRBIT expression in HeLa cells causes imbalanced dNTP pools and altered cell cycle progression. Under normal physiological conditions, where ATP levels are high, such inhibition can only be achieved when binding of IRBIT is strengthened by phosphorylation
-
isopropylideneadenosylcobalamin
-
-
Mg2+
-
strongly inhibitory in absence of ATP
N',3,4,5-tetrahydroxybenzenecarboximidamide
-
i.e. trimidox, highly synergistic effects of simultaneous treatment of cells with inhibitors gallic acid and trimidox
N-hydroxy-N'-(3,4,5-trimethoxyphenyl)-3,4,5-trimethoxybenzamidine
-
a resveratrol analogue, inhibits the enzyme in HL-60 cells showing synergistic effects with arabinofuranosylcytosine in antitumor activity, overview
nebularylcobalamin
-
-
signalosome protein complex COP9
i.e. CSN, is a negative regulator of RNR2 activity in Arabidopsis thaliana. The pleiotropic regulator of plant development and contains eight-subunits, RNR2 binds to the C-terminus of subunit 7, CSN7; i.e. CSN, is a negative regulator of RNR2 activity in Arabidopsis thaliana. The pleiotropic regulator of plant development and contains eight-subunits, RNR2 binds to the C-terminus of subunit 7, CSN7
-
triapine
tubercidylcobalamin
-
-
[3-(adenosin-5'-O-yl)propyl]cobalamin
-
-
[4-(adenosin-5'-O-yl)butyl]cobalamin
-
-
[5-(adenosin-5'-O-yl)pentyl]cobalamin
-
-
[6-(adenosin-5'-O-yl)hexyl]cobalamin
-
-
[7-(adenosin-5'-O-yl)heptyl]cobalamin
-
-
[omega-(adenosin-5'-O-yl)alkyl]cobalamin
-
-
additional information
-
no enzyme inhibition by arabinoside cytosine
-