Information on EC 1.17.4.1 - ribonucleoside-diphosphate reductase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.17.4.1
-
RECOMMENDED NAME
GeneOntology No.
ribonucleoside-diphosphate reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenosine deoxyribonucleotides de novo biosynthesis
-
-
adenosine deoxyribonucleotides de novo biosynthesis II
-
-
Glutathione metabolism
-
-
guanosine deoxyribonucleotides de novo biosynthesis I
-
-
guanosine deoxyribonucleotides de novo biosynthesis II
-
-
Metabolic pathways
-
-
purine metabolism
-
-
Purine metabolism
-
-
pyrimidine deoxyribonucleotides biosynthesis from CTP
-
-
pyrimidine deoxyribonucleotides de novo biosynthesis I
-
-
pyrimidine deoxyribonucleotides de novo biosynthesis III
-
-
pyrimidine deoxyribonucleotides de novo biosynthesis IV
-
-
pyrimidine metabolism
-
-
Pyrimidine metabolism
-
-
superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. coli)
-
-
SYSTEMATIC NAME
IUBMB Comments
2'-deoxyribonucleoside-diphosphate:thioredoxin-disulfide 2'-oxidoreductase
This enzyme is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. An iron protein. While the enzyme is activated by ATP, it is inhibited by dATP [3,6].
CAS REGISTRY NUMBER
COMMENTARY hide
9047-64-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
Bacillus anthracis ATCC 14579
-
UniProt
Manually annotated by BRENDA team
strain ATCC 14579
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
nrdA and nrdB genes encoding a CDP reductase are induced by oxidative stress
-
-
Manually annotated by BRENDA team
strain R163, gene nrdF encoding subunit R2F
-
-
Manually annotated by BRENDA team
strain R163, gene nrdF encoding subunit R2F
-
-
Manually annotated by BRENDA team
Chinese hamster overy cells
-
-
Manually annotated by BRENDA team
genes nrdE and nrdF encoding the subunits alpha2 and beta2
-
-
Manually annotated by BRENDA team
Escherichia coli K-12 CM735
genes nrdA and nrdB encoding subunits R1 and R2, respectively
-
-
Manually annotated by BRENDA team
Escherichia coli overproducing
overproducing strain
-
-
Manually annotated by BRENDA team
Herpes simplex virus
an oncovirus belonging to the gamma-subfamily of human herpesviruses
-
-
Manually annotated by BRENDA team
strain MHOM/IN/1983/AG83
-
-
Manually annotated by BRENDA team
Leishmania donovani MHOM/IN/1983/AG83
strain MHOM/IN/1983/AG83
-
-
Manually annotated by BRENDA team
strain strain H37Rv, gene Rv3051c
-
-
Manually annotated by BRENDA team
3D7
-
-
Manually annotated by BRENDA team
monkey kidney cells BSC-40 induced by vaccina virus strain WR, activity may be virally encoded
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
Uniprot
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
wild-type plants exposed to a low concentration of an RNR inhibitor, hydroxyurea, produce chlorotic leaves without growth retardation, reminiscent of v3 and st1 mutants. Upon insufficient activity of RNR, plastid DNA synthesis is preferentially arrested to allow nuclear genome replication in developing leaves, leading to continuous plant growth; wild-type plants exposed to a low concentration of an RNR inhibitor, hydroxyurea, produce chlorotic leaves without growth retardation, reminiscent of v3 and st1 mutants. Upon insufficient activity of RNR, plastid DNA synthesis is preferentially arrested to allow nuclear genome replication in developing leaves, leading to continuous plant growth
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-methyladenosine 5'-diphosphate + reduced dithiothreitol
adenine + 2'-deoxy-2'-methyladenosine + H2O
show the reaction diagram
-
-
5% reduction to 2'-deoxy-2'-methyladenosine, adenine is the major product besides other unidentified products
?
2'-methyluridine 5'-diphosphate + reduced dithiothreitol
uracil + H2O + ?
show the reaction diagram
-
-
uracil is the major product, unidentified minor product may be 2'-deoxy-2'-methyluridine
?
2,6-diaminopurineriboside diphosphate + reduced thioredoxin
2'-deoxy-2,6-diaminopurineriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
2-aminopurineriboside diphosphate + reduced thioredoxin
2'-deoxy-2-aminopurineriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
8-vinyl-ADP + reduced thioredoxin
8-vinyl-2'-deoxy-ADP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ADP + dithiothreitol
2'-dADP + oxidized dithiothreitol + H2O
show the reaction diagram
-
-
-
?
ADP + reduced thioredoxin
2'-dADP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ADP + reduced thioredoxin
2'-deoxy-ADP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
benzimidazoleriboside diphosphate + reduced thioredoxin
2'-deoxybenzimidazolriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
CDP + dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
CDP + reduced dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
CDP + reduced thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
CDP + reduced thioredoxin
2'-deoxy-CDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
CDP + thioredoxin
dCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin A
2'-dCDP + thioredoxin A disulfide + H2O
show the reaction diagram
CDP + thioredoxin YosR
2'-dCDP + thioredoxin YosR disulfide + H2O
show the reaction diagram
CTP + reduced thioredoxin
2'-dCTP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
dCDP + DTT disulfide + H2O
CDP + DTT
show the reaction diagram
GDP + reduced thioredoxin
2'-deoxy-GDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
GDP + reduced thioredoxin
2'-dGDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
?
GDP + thioredoxin
2'-deoxyGDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
nucleoside 5'-diphosphate + NrdH-redoxin
2'-deoxynucleoside 5'-diphosphate + NrdH-redoxin disulfide + H2O
show the reaction diagram
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
purineriboside diphosphate + reduced thioredoxin
2'-deoxypurineriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
ribonucleoside diphosphate + reduced glutaredoxin
2'-deoxyribonucleoside diphosphate + oxidized glutaredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced glutaredoxin 1
2'-deoxyribonucleoside diphosphate + oxidized glutaredoxin 1 + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
tubercidin diphosphate + reduced thioredoxin
2'-deoxytubercidin diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
14% of GDP reduction rate
-
?
UDP + reduced thioredoxin
2'-deoxy-UDP + oxidized thioredoxin + H2O
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
GDP + thioredoxin
2'-deoxyGDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
nucleoside 5'-diphosphate + NrdH-redoxin
2'-deoxynucleoside 5'-diphosphate + NrdH-redoxin disulfide + H2O
show the reaction diagram
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5'-deoxyadenosylcobalamin
-
class II enzymes
adenosylcobalamin
absolutely requires adenosylcobalamin (as a radical generator) for activity, KM: 0.001 mM
Cobalamin
diferric(III)-tyrosyl radical cofactor
dimanganese(III)-tyrosyl radical cofactor
Fe2 III/III-Y radical cofactor
-
assembly, maintenance, and role in catalysis of the Fe2 III/III-Y radical cofactor of Ecbeta2 subunit, structure modelling, detailed overview
-
FMN
binding structure analysis with NrdF and NrdI, NrdF contributes to the electrostatic environment of the FMN binding pocket, overview
glutaredoxin
manganese-iron cofactor
Mn-Fe cofactor
-
the R2 protein of class I RNR contains a Mn-Fe instead of the standard Fe-Fe cofactor. Ct R2 has a redox-inert phenylalanine replacing the radical-forming tyrosine of classic RNRs, which implies a different mechanism of O2 activation, overview
-
Mn/Fe redox cofactor
unusual cofactor instead of Fe-Fe cofactor in other RNRs. Assembly, maintenance, and role in catalysis of the MnIV/FeIII cofactor of Ctbeta2 subunit, structure modelling, detailed overview
-
MnIV/FeIII cofactor
-
electron transfer mechanism and conformational identification, role in reaction and mechanism, detailed overview
-
NrdH-redoxin
T4 thioredoxin
thioredoxin
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
activity depends on Ca2+
Fe
-
class I enzymes contain diferric(III)-tyrosyl radical cofactor
Manganese
Mn(IV)
-
MnIV/FeIII cofactor
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(-)-epicatechin
(2E)-2-(anthracen-9-ylmethylidene)-N-hydroxyhydrazinecarboximidamide
-
i.e. ABNM-13, application leads to significant alterations of deoxyribonucleoside triphosphate pool balance and a highly significant decrease of incorporation of radiolabeled cytidine into DNA of HL-60 cells. Diminished ribonucleotide reductase activity causes replication stress which is consistent with activation of Chk1 and Chk2, resulting in downregulation/degradation of Cdc25A. Cdc25B is upregulated, leading to dephosphorylation and activation of Cdk1. The combined disregulation of Cdc25A and Cdc25B is the most likely cause for ABNM-13 induced S-phase arrest
(E)-2'-fluoromethylene-2'-deoxycytidine-5-diphosphate
-
i.e. N3dNDP, inhibitor forming a furanone intermediate. Modeling of enzyme-inhibitor complex
1,10-phenanthroline
1-Formylisoquinoline thiosemicarbazone
-
; 0.0006 mM, 81% inhibition, 0.1 mM desferal reverses inhibition
1-methyl-1-hydroxyurea
-
10 mM, 55% inhibition
2',3'-dideoxy-ATP
-
less potent inhibitor than dATP, 0.1 mM, 50% inhibition of CDP reduction
2'-azido-2'-deoxynucleotides
-
-
2'-chloro-2'-deoxycytidine 5'-diphosphate
-
-
2'-deoxy-2'-azidocytidine diphosphate
2'-halo-2'-deoxynucleotides
-
-
2'-methyladenosine 5'-diphosphate
-
probably mechanism based inhibition, competitive inhibition vs. ADP and GDP
2'-methyluridine 5'-diphosphate
-
probably mechanism based inhibition, competitive inhibition vs. UDP and CDP
2,3,4-Trihydroxybenzamide
-
-
2,3,4-trihydroxybenzohydroxamic acid
2,3-Dihydro-1H-pyrazolo[2,3-a]imidazole
2,3-dihydroxybenzohydroxamic acid
-
0.008 mM, 50% inhibition
2,4-dichlorobenzohydroxamic acid
-
0.45 mM, 50% inhibition
2,4-dihydroxybenzohydroxamic acid
-
0.3 mM, 50% inhibition
2,5-dihydroxybenzohydroxamic acid
-
0.2 mM, 50% inhibition
2,6-dihydroxybenzohydroxamic acid
-
0.1 mM, 50% inhibition
2-(diphenylmethylidene)-N,N-dimethylhydrazinecarbothioamide
-
metal chelator, significantly decreases ribonucleotide reductase activity, whereas the NADPH/NADP+ total ratio is not reduced
2-acetylpyridine N,N-dimethylthiosemicarbazonato-N,N,S-dichlorogallium(III)
-
-
2-acetylpyridine N-pyrrolidinylthiosemicarbazonato-N,N,S-dichlorogallium(III)
-
-
2-aminobenzohydroxamic acid
-
0.12 mM, 50% inhibition
2-azido-UDP
-
rapid time dependent inactivation
2-furan-3-ylbenzaldehyde N-(4-hydroxyphenyl)thiosemicarbazone
-
-
2-furan-3-ylbenzaldehyde N-phenylthiosemicarbazone
-
-
2-hydroxy-3-methylbenzohydroxamic acid
-
0.15 mM, 50% inhibition
2-hydroxy-4-aminobenzohydroxamic acid
-
0.2 mM, 50% inhibition
2-hydroxybenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
-
2-hydroxybenzaldehyde N-phenylthiosemicarbazone
-
-
2-hydroxybenzohydroxamic acid
-
0.15 mM, 50% inhibition
2-Nitro-imidazole
-
trivial name azomycin
2-thiophen-2-ylbenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
-
2-thiophen-2-ylbenzaldehyde N-phenylthiosemicarbazone
-
-
2-[di(pyridin-2-yl)methylidene]-N,N-dimethylhydrazinecarbothioamide
-
metal chelator, significantly decreases ribonucleotide reductase activity, whereas the NADPH/NADP+ total ratio is not reduced
3,4,5-Trihydroxybenzamide
-
-
3,4,5-Trihydroxybenzohydroxamic acid
3,4,5-Trihydroxybenzoic acid
-
-
3,4,5-trihydroxyhydroxamic acid
-
0.012 mM, 50% inhibition, reversible
-
3,4,5-trimethoxybenzohydroxamic acid
-
0.1 mM, 50% inhibition
3,4-diaminobenzohydroxamic acid
-
0.04 mM, 50% inhibition
3,4-dichlorobenzohydroxamic acid
-
0.3 mM, 50% inhibition
3,4-Dihydroxybenzamide
-
-
3,4-dihydroxybenzohydroxamic acid
3,4-dimethoxybenzohydroxamic acid
-
0.3 mM, 50% inhibition
3,4-dimethylbenzohydroxamic acid
-
0.3 mM, 50% inhibition
3,5-diamino-1H-1,2,4-triazole
3,5-diaminopyridine-2-carboxaldehyde thiosemicarbazone
-
-
3,5-dihydroxybenzohydroxamic acid
-
0.4 mM, 50% inhibition
3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone
-
-
3-aminobenzohydroxamic acid
-
0.35 mM, 50% inhibition
3-aminopyridine-2-carboxaldehyde thiosemicarbazone
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-hydroxybenzohydroxamic acid
-
0.35 mM, 50% inhibition
3-methyl aminopyridine-2-carboxaldehyde thiosemicarbazone
-
-
3-methyl-1-hydroxyurea
-
10 mM, 57% inhibition
3-Methyl-4-nitrophenol
-
-
4-Amino-2-phenylimidazole-5-carboxamide
-
-
4-aminobenzohydroxamic acid
-
0.15 mM, 50% inhibition
4-dimethylaminobenzohydroxamic acid
-
0.5 mM, 50% inhibition
4-hydroxy-3-methoxybenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
-
4-hydroxy-3-methoxybenzaldehyde N-phenylthiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(2-chlorophenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(2-hydroxyphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(2-methoxyphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(2-methylphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(2-nitrophenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(3-chlorophenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(3-hydroxyphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(3-methylphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(4-hydroxyphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(4-methylphenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-(4-nitrophenyl)thiosemicarbazone
-
-
4-hydroxybenzaldehyde N-phenylthiosemicarbazone
-
-
4-hydroxybenzohydroxamic acid
-
0.30 mM, 50% inhibition
4-methoxybenzohydroxamic acid
-
0.5 mM, 50% inhibition
4-methoxyphenol
-
-
4-Methyl-5-amino isoquinoline-1-carboxaldehyde thiosemicarbazone
4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone
4-methylaminobenzohydroxamic acid
-
0.33 mM, 50% inhibition
4-nitrobenzohydroxamic acid
-
0.5 mM, 50% inhibition
5-(1-Aziridinyl)-2,4-dinitrobenzamide
5-amino-4-morpholinomethylpyridine-2-carboxaldehyde thiosemicarbazone
-
-
5-aminopyridine-2-carboxaldehyde thiosemicarbazone
-
-
5-hydroxy-4-methyl-1-formylisoquinoline thiosemicarbazone
-
-
5-methyl-4-amino-1-formylisoquinoline thiosemicarbazone
-
-
6-chloro-9H-(3-C-methyl-2,3-di-O-acetyl-5-O-benzoyl-beta-D-ribofuranosyl)purine
-
-
8-hydroxyquinoline
8-hydroxyquinoline 5-sulfonate
Acetohydroxamic acid
aurintricarboxylate
bathophenanthroline disulfonate
bathophenanthroline sulfonate
benzohydroxamic acid
-
0.4 mM, 50% inhibition
butylphenyl-dGTP
-
0.13 mM, 50% inhibition of ADP reduction
caracemide
Catechol derivatives
-
-
-
chlorambucil
Cibacron blue F3 GA
-
-
cisplatin
clofarabine
-
an adenosine analogue is used in the treatment of refractory leukemias. Its mode of cytotoxicity is associated in part with the triphosphate functioning as an allosteric reversible inhibitor of hRNR, rapid inactivation
clofarabine diphosphate
-
ClFDP, a C-site slow-binding, reversible inhibitor, mechanism of inhibition via altering the quaternary structure of the large subunit of RNR, overview. Binds also mutant D57N-alpha subunit. CDP protects against inhibition
clofarabine triphosphate
-
ClFTP, an A-site rapidly binding reversible inhibitor, mechanism of inhibition via altering the quaternary structure of the large subunit of RNR, overview. Neither CDP (C site) nor dGTP (A site) had any effect on inhibition by ClFTP
dADP
-
product inhibition
dCDP
-
product inhibition
deferoxamine mesylate
desferrioxamine
-
-
dGDP
-
product inhibition
dithiothreitol
-
higher than 10 mM, activation below
dITP
-
inhibition of CDP reduction
dUDP
-
product inhibition
dUTP
-
inhibition of: CDP reduction, UDP reduction
ethyleneglycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid
-
trivial name EGTA
Fmoc(NCH3)PhgLDChaDF
-
inhibitor identified by competition with inhibitor N-AcFTLDADF and inhibition of enzyme activity
FmocWFDF
-
inhibitor identified by competition with inhibitor N-AcFTLDADF and inhibition of enzyme activity
FmocWVFF
-
inhibitor identified by competition with inhibitor N-AcFTLDADF and inhibition of enzyme activity
formohydroxamic acid
-
10 mM, 43% inhibition
FTLDADF
-
last seven amino acid residues of carboxyl terminus of the R2 subunit of mouse enzyme and its N-alpha-acetyl derivative inhibit thymus enzyme
-
gamma-L-Glutaminyl-4-hydroxybenzene
-
naturally occuring quinol from spores of Agaricus bisporus, 0.76 mM, 50% inhibition
gemcitabine
glutaminyl-3,4-dihydroxybenzene
-
1.23 mM, 50% inhibition
glutathione
-
analogs with aromatic substituents
H2O2
-
0.01%, 81% inhibition
hydroxylamine
-
10 mM, complete inhibition
Hydroxyurea
Isoquinoline-1-carboxaldehyde thiosemicarbazone
L-ADP
-
inhibition of D-ADP reduction, competitive inhibition of dGTP-dependent D-ADP reductase
mammalian R2 C-terminal heptapeptide P7
-
Ac-1FTLDADF7, the inhibitor binds at bind at a contiguous site containing residues that are highly conserved among eukaryotes, binding structure, overview
meso-alpha,beta-Diphenylsuccinate
-
-
Methyl 3,4,5-trihydroxybenzoate
-
-
monoclonal antibody raised against yeast tubulin
-
CDP reductase activity is inhibited to a greater extent than ADP, UDP or GDP reductase activity, antibody recognizes a specific sequence in the C-terminal region on the R2 subunit
-
N-AcFTLDADF
-
heptapeptide inhibitor based on subunit R2 C-terminus
N-alpha-acetyl-FTLDADF
-
-
N-ethylmaleimide
-
0.1 mM, 50% inhibition of intact enzyme, 0.05 mM, 50% inhibition of effector-binding subunit, 0.3 mM, 50% inhibition of non-heme iron subunit
n-Hexanohydroxamic acid
-
-
N-Hydroxy-alpha-aminoheptanoate
-
5 mM, 50% inhibition
N-Hydroxy-alpha-aminohexanoate
-
15 mM, 50% inhibition
N-hydroxyguanidine
-
10 mM, 89% inhibition
N-hydroxyurethane
-
10 mM, 66% inhibition
N-Methyl 3,4,5-trihydroxybenzamide
-
-
N-Methylhydroxylamine
N-[[(3S,5S,7S,7aS)-7-([[3-(9H-fluoren-9-yl)propanoyl]oxy]methyl)-3-hydroxy-5-(2-methylpropoxy)hexahydropyrano[3,4-b]pyrrol-1(2H)-yl]acetyl]-L-alpha-aspartyl-L-phenylalanine
-
50% inhibition at 0.04-0.05 mM, bicyclic scaffold is necessary to maintain inhibitory activity
N6-(2-furanylmethyl)-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
-
-
N6-(2-thienylmethyl)-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
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N6-(3-pyrazolyl)-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
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N6-cyclobutyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
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N6-cycloheptyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
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N6-endo-norbonyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
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N6-phenyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
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nicotinohydroxamic acid
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0.8 mM, 50% inhibition
NSFTLDADF
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inhibition of CDP reductase activity, peptide corresponds to the C-terminal region of the R2 subunit and competes with binding of R2 to the R1 subunit
nucleotide analogs
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overview
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o-ClBzocFc[ELDK]DF
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inhibitor identified by competition with inhibitor N-AcFTLDADF and inhibition of enzyme activity
p-chloromercuribenzoate
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0.35 mM, 50% inhibition of intact enzyme, 0.15 mM, 50% inhibition of effector-binding subunit, 1.5 mM, 50% inhibition of non-heme iron subunit
peptide P6
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1Fmoc(Me)PhgLDChaDF7, the inhibitor binds at a contiguous site containing residues that are highly conserved among eukaryotes. The Fmoc group in P6 peptide forms several hydrophobic interactions that contribute to its enhanced potency in binding to ScR1, binding structure, overview
peptide Y-R2C19
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a 20-mer peptide, which is identical to the C-terminal peptide tail of the R2 subunit and is a known competitive inhibitor of binding of the native R2 protein to R1
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Periodate-oxidized inosine
phenylacetohydroxamic acid
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1 mM, 50% inhibition
picolinohydroxamic acid
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0.5 mM, 50% inhibition
Polyhydroxybenzohydroxamic acid
pyrazoloimidazol
Pyridine-2-carboxaldehyde thiosemicarbazone
pyridoxal 5'-phosphate
Herpes simplex virus
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1 mM, 65% inhibition, 3 mM, 90% inhibition
pyridoxal 5'-phosphate/NaBH4
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Pyrogallol derivatives
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quercetin
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i.e. 3,3',4',5,7-pentahydroxyflavone, isolated from air-dried powdered leaves of Vitex negundo, a lipophilic metal chelator, that interferes with the parasite's iron metabolism inhibiting Fe2+ acquisition from an endogenous source, combination of quercetin with serum albumin increases its bioavailability, the inhibitor causes deprivation of the enzyme of iron which in turn destabilized the critical tyrosyl radical required for its catalysing activity
Sml1
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inhibitor protein Sml1 competes with the C-terminal domain of subunit R1 for association with its N-terminal domain to hinder the accessibility of the CX2C motif to the active site for R1 regeneration during the catalytic cycle
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Sml1 protein
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a 104-residue Saccharomyces cerevisiae protein, inhibits ribonucleotide reductase activity by binding to the R1 subunit interacting with the N-terminal domain of R1, R1-NTD, which involves a conserved two-residue sequence motif in the R1-NTD, the Sml1-R1 interaction causes SML1-dependent lethality, overview
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Sodium arsenite
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0.025 mM, almost complete inhibition of CDP reduction, 86% inhibition of GDP reduction
Synthetic peptides
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which specifically inhibit the activity of virus-induced enzyme
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Thenoyltrifluoroacetone
triapine
YAGAVVNDL
Herpes simplex virus
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peptide may prevent association of the two subunits by competing for the subunit binding site
YGAVVNDL
Herpes simplex virus
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[bis(2-acetylpyridine N,N-dimethylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
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[bis(2-acetylpyridine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
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[bis(2-acetylpyridine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
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[bis(2-acetylpyridine N-pyrrolidinylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
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[bis(2-acetylpyridine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
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[bis(2-acetylpyridine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
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[bis(acetylpyrazine N,N-dimethylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
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[bis(acetylpyrazine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
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[bis(acetylpyrazine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
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[bis(acetylpyrazine N-piperidinylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
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[bis(acetylpyrazine N-piperidinylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
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[bis(acetylpyrazine N-piperidinylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
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[bis(acetylpyrazine N-pyrrolidinylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
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[bis(acetylpyrazine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
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[bis(acetylpyrazine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
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[FeCl4] 2-acetylpyridine N,N-dimethylthiosemicarbazone
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Ga(III) and Fe(III) complexes destroy the tyrosyl radical of the presumed target ribonucleotide reductase
[FeCl4] 2-acetylpyridine N-pyrrolidinylthiosemicarbazone
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[FeCl4] acetylpyrazine N,N-dimethylthiosemicarbazone
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[FeCl4] acetylpyrazine N-piperidinylthiosemicarbazone
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[FeCl4] acetylpyrazine N-pyrrolidinylthiosemicarbazone
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[GalCl2] 2-acetylpyridine N,N-dimethylthiosemicarbazone
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Ga(III) and Fe(III) complexes destroy the tyrosyl radical of the presumed target ribonucleotide reductase
[GalCl2] 2-acetylpyridine N-pyrrolidinylthiosemicarbazone
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[GalCl2] acetylpyrazine N,N-dimethylthiosemicarbazone
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[GalCl2] acetylpyrazine N-piperidinylthiosemicarbazone
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[GalCl2] acetylpyrazine N-pyrrolidinylthiosemicarbazone
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additional information