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
1.17.4.1
-
RECOMMENDED NAME
GeneOntology No.
ribonucleoside-diphosphate reductase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
proposed mechanism
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
postulated mechanism, radical cation intermediates; proposed mechanism
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
proposed mechanism
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
NDP reduction requires cleavage of the 3'-C-H bond of the substrate, hypothesis of enzyme mechanism
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
allosteric regulation of the catalytic activity of subunit R1
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
kinetics and mechanism of formation of the tyrosyl radical and micro-oxo-diiron cluster in the R2 subunit
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
presence of divalent cations mediates a rapid radical-transfer equilibrium between W48 and Y356. Cation-mediated propagation of the radical from W48 to Y356 gives rise to a fast phase of Y radical production that is essentially coincident with W48 cation radical formation and creates an efficient pathway for decay of W48 cation radical
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
role of enzyme in second step of catalytic mechanism which corresponds to the protonation/elimination of the substrates C2 hydroxyl group is mainly entropic by placing the substrate and the two reactive residues in a position that allows for the highly favorable concerted trimolecular reaction, and to protect the enzyme radical from the solvent
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
binding of specificity effector rearranges loop 2 and moves residue P294 out of the catalytic site, accomodating substrate binding. substrate binding further rearranges loop2. Cross-talk occurs largely through R293 and Q288 of loop 2. Substrate ribose binds with its 3 hydroxyl closer than its 2 hydroxyl to residue C218 of the catalytic redox pair
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
reaction involves formation of a keto-deoxyribonucleotide intermediate. In case of furanone inhibitors, the intermediate dissociates from the active site, depending on the solvation free energy of the 2-substituents, its influence inside the active site, and the charge transfer mechanism from a protein side chain to solution as thermodynamic driving forces. Substrates do not dissociate from the active site but complete the catalytic cycle
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
catalytic mechanism
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
reaction mechanism via formation of a tyrosyl radical at Tyr356 od subunit R1, model for radical transport in which there is a unidirectional transport of the electron and proton transport among residues of R1
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
reaction mechanism, two possible pathways, overview
-
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
adenosine deoxyribonucleotides de novo biosynthesis
-
adenosine deoxyribonucleotides de novo biosynthesis II
-
guanosine deoxyribonucleotides de novo biosynthesis I
-
guanosine deoxyribonucleotides de novo biosynthesis II
-
pyrimidine deoxyribonucleotides biosynthesis from CTP
-
pyrimidine deoxyribonucleotides de novo biosynthesis I
-
pyrimidine deoxyribonucleotides de novo biosynthesis III
-
pyrimidine deoxyribonucleotides de novo biosynthesis IV
-
superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. coli)
-
Purine metabolism
-
Pyrimidine metabolism
-
Glutathione metabolism
-
Metabolic pathways
-
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase
-
-
-
-
ADP reductase
-
-
-
-
CDP reductase
-
-
-
-
class I ribonucleotide reductase
-
-
class I ribonucleotide reductase
-
-
class I ribonulceotide reductase
-
-
class I RNR
Escherichia coli K-12 CM735
-
-
-
class I RNR
-
-
class I RR
-
-
class Ia ribonucleotide reductase
-
-
class Ia RNR
-
-
class Ia RR
-
-
class Ib ribonucleotide reductase
-
-
class Ib ribonucleotide reductase
Bacillus subtilis JH624
-
-
-
class Ib ribonucleotide reductase
-
-
class Ib ribonucleotide reductase
P37146
-
class Ib ribonucleotide reductase
Escherichia coli GR536
-
-
-
class Ib RNR
-
-
class Ib RNR
-
-
class Ib RNR
Bacillus subtilis JH624
-
-
-
class Ib RNR
P37146
-
class Ib RNR
Escherichia coli GR536
-
-
-
class Ic ribonucleotide reductase
-
-
manganese-ribonucleotide reductase
-
-
manganese-ribonucleotide reductase
Corynebacterium glutamicum R163
-
-
-
NrdA
P00452
-
NrdA
Escherichia coli K-12 CM735
-
-
-
NrdB
Escherichia coli K-12 CM735
-
-
-
NrdE
Q81G56
-
NrdE
Bacillus anthracis ATCC 14579
Q81G56
-
-
NrdE
Bacillus subtilis JH624
-
-
-
NrdE
P39452
-
NrdE
Escherichia coli GR536
-
-
-
NrdF
Bacillus subtilis JH624
-
-
-
NrdF
Escherichia coli GR536
-
-
-
nucleoside diphosphate reductase
-
-
-
-
p53-inducible ribonucleotide reductase
-
-
reductase, ribonucleoside diphosphate
-
-
-
-
ribonucleoside 5'-diphosphate reductase
-
-
-
-
ribonucleoside diphosphate reductase
-
-
-
-
ribonucleoside-diphosphate reductase subunit M2 B
Q7LG56
-
ribonucleotide diphosphate reductase
-
-
-
-
ribonucleotide reductase
-
-
-
-
ribonucleotide reductase
P50651, Q6Y657, Q9LSD0
-
ribonucleotide reductase
-
-
ribonucleotide reductase
-
-
ribonucleotide reductase
-
-
ribonucleotide reductase
-
-
ribonucleotide reductase
Q5VRJ6, Q6K848
-
ribonucleotide reductase
-
-
ribonucleotide reductase
P95484
-
ribonucleotide reductase
-
-
RIR2
P31350
-
RNR
Escherichia coli K-12 CM735
-
-
-
RNR
Q5VRJ6, Q6K848
-
RNR1 rRibonucleoside-diphosphate reductase large chain 1
P21524
-
RNR2
P50651, Q6Y657, Q9LSD0
-
UDP reductase
-
-
-
-
Mn-RNR
Corynebacterium glutamicum R163
-
-
-
additional information
-
a class I ribonucleotide reductase
additional information
-
a class Ic ribonucleotide reductase
additional information
-
class I ribonucleotide reductase
CAS REGISTRY NUMBER
COMMENTARY
9047-64-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
small subunit A, R2A; var. Columbia, ecotype Columbia-0, three AtRNR2-like catalytic subunit genes AtTSO2, AtRNR2A, and AtRNR2B
UniProt
Manually annotated by BRENDA team
small subunit B, R2B; var. Columbia, ecotype Columbia-0, three AtRNR2-like catalytic subunit genes AtTSO2, AtRNR2A, and AtRNR2B
Q6Y657
SwissProt
Manually annotated by BRENDA team
small subunit C, TSO2; var. Columbia, ecotype Columbia-0, three AtRNR2-like catalytic subunit genes AtTSO2, AtRNR2A, and AtRNR2B
UniProt
Manually annotated by BRENDA team
Bacillus anthracis ATCC 14579
-
UniProt
Manually annotated by BRENDA team
strain ATCC 14579
-
-
Manually annotated by BRENDA team
Bacillus subtilis JH624
-
-
-
Manually annotated by BRENDA team
nrdA and nrdB genes encoding a CDP reductase are induced by oxidative stress
-
-
Manually annotated by BRENDA team
calf
-
-
Manually annotated by BRENDA team
a human pathogen
-
-
Manually annotated by BRENDA team
class Ib reductase
UniProt
Manually annotated by BRENDA team
strain ATCC 6872, gene nrdF
-
-
Manually annotated by BRENDA team
strain R163, gene nrdF encoding subunit R2F
-
-
Manually annotated by BRENDA team
Corynebacterium glutamicum R163
strain R163, gene nrdF encoding subunit R2F
-
-
Manually annotated by BRENDA team
Chinese hamster overy cells
-
-
Manually annotated by BRENDA team
enzyme induced in Escherichia coli by infection with bacteriophage T4
-
-
Manually annotated by BRENDA team
may use triphosphates as substrates
-
-
Manually annotated by BRENDA team
genes nrdA and nrdB encoding subunits R1 and R2, respectively
-
-
Manually annotated by BRENDA team
genes nrdE and nrdF encoding the subunits alpha2 and beta2
-
-
Manually annotated by BRENDA team
isoform NrdA
UniProt
Manually annotated by BRENDA team
isoform NrdE
UniProt
Manually annotated by BRENDA team
overproducing strain
-
-
Manually annotated by BRENDA team
use of crystal structure for modeling of active site
-
-
Manually annotated by BRENDA team
Escherichia coli GR536
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
-
-
-
Manually annotated by BRENDA team
Herpes simplex virus
type 1, HSV-1
-
-
Manually annotated by BRENDA team
Herpes simplex virus
type 2, HSV-2
-
-
Manually annotated by BRENDA team
adults with refractory acute leukemias and aggressive myeloproliferative disorders, MPD
-
-
Manually annotated by BRENDA team
HeLa cells
-
-
Manually annotated by BRENDA team
isoform p53R2
SwissProt
Manually annotated by BRENDA team
Molt 4F cells
-
-
Manually annotated by BRENDA team
patients with advanced myeloid leukemia
-
-
Manually annotated by BRENDA team
ribonucleoside-diphosphate reductase subunit M2 B
SwissProt
Manually annotated by BRENDA team
small subunit RIR2
UniProt
Manually annotated by BRENDA team
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
baby hamster kidney cells, enzyme induced by Herpes simplex, virus type 1, HSV-1
-
-
Manually annotated by BRENDA team
female BALB/c mice and A/J mice
-
-
Manually annotated by BRENDA team
M2 subunit; BALB/3T3 cells, ATCC CCL 163
SwissProt
Manually annotated by BRENDA team
mutant line of T-lymphoma S49 cells
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
wild-type and reductase inhibitor resistant L1210 cell line
-
-
Manually annotated by BRENDA team
strain strain H37Rv, gene Rv3051c
-
-
Manually annotated by BRENDA team
large subunit, gene V3; subsp. japonica, genes virescent3, V3, and stripe1, Str1, encoding the large and small subunits, RNRL1, and RNRS1
UniProt
Manually annotated by BRENDA team
small subunit, gene Str1; subsp. japonica, genes virescent3, V3, and stripe1, Str1, encoding the large and small subunits, RNRL1, and RNRS1
UniProt
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
enzyme is a complex of the NrdA protein harboring the active site and the allosteric sites and the NrdB protein harboring a tyrosyl radical
-
-
Manually annotated by BRENDA team
-
P95484
SwissProt
Manually annotated by BRENDA team
Morris hepatoma cells; Novikoff hepatoma cells
-
-
Manually annotated by BRENDA team
non-proliferating cells inactivate 88000-90000 Da M1 subunit by degradation into 40000 Da fragments
-
-
Manually annotated by BRENDA team
Novikoff hepatoma cells
-
-
Manually annotated by BRENDA team
large subunit 1
Uniprot
Manually annotated by BRENDA team
modulation of concentration of tyrosyl radicals is not involved in the regulation of enzyme activity
-
-
Manually annotated by BRENDA team
serovar Typhimurium, inside RAW264.7 macrophages or HeLa cells
-
-
Manually annotated by BRENDA team
Scenedesmus obliquus
-
-
-
Manually annotated by BRENDA team
Scenedesmus obliquus
green algae
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
the enzyme is involved in DNA replication and damage repair, respectively
physiological function
-
hp53R2 possibly plays a regulatory role in iron assimilation
physiological function
Q5VRJ6, Q6K848
RNR regulates the rate of deoxyribonucleotide production for DNA synthesis and repair. Rice virescent3 and stripe1 encoding the large and small subunits of ribonucleotide reductase are required for chloroplast biogenesis during early leaf development; RNR regulates the rate of deoxyribonucleotide production for DNA synthesis and repair. Rice virescent3 and stripe1 encoding the large and small subunits of ribonucleotide reductase are required for chloroplast biogenesis during early leaf development
physiological function
P50651, Q6Y657, Q9LSD0
RNR is an essential enzyme that provides dNTPs for DNA replication and repair, AtRNR2A induction is likely required for the replicative stress checkpoint. Individual RNR2-like catalytic subunit genes participate in unique aspects of the cellular response to DNA damage in Arabidopsis thaliana; RNR is an essential enzyme that provides dNTPs for DNA replication and repair. Individual RNR2-like catalytic subunit genes participate in unique aspects of the cellular response to DNA damage in Arabidopsis thaliana; RNR is an essential enzyme that provides dNTPs for DNA replication and repair, TSO2 and E2Fa are likely required for the DNA damage response. Individual RNR2-like catalytic subunit genes participate in unique aspects of the cellular response to DNA damage in Arabidopsis thaliana
physiological function
-
the allosterically regulated enzyme is responsible for the reduction of all four ribonucleotides to their corresponding deoxyribonucleotides, dNTPs, which are the building blocks of DNA. This reaction involves a free radical, the activity of RNR regulates the cellular levels of the dNTP pool, ensuring that precise DNA replication and repair occurs
physiological function
-
Escherichia coli class Ib RNR converts nucleoside 5'-diphosphates to deoxynucleoside 5'-diphosphates and is expressed under iron-limited and oxidative stress conditions
physiological function
-
class Ib RNR converts nucleoside 5'-diphosphates to deoxynucleoside 5'-diphosphates in iron-limited and oxidative stress conditions
physiological function
-
RNRs catalyze the conversion of nucleotides UDP, ADP, GDP, and CDP to deoxynucleotides, providing the monomeric building blocks required for DNA replication and repair
physiological function
-
ribonucleoside diphosphate reductase is an essential enzyme for the biosynthesis of the four dNTP in all living cells
physiological function
-
role of RNRs during infection of macrophages and epithelial cells, overview. Class Ia to be mainly responsible for deoxyribonucleotide production during invasion and proliferation inside macrophages and epithelial cells, while class Ib RNR is not. Class Ib RNR may contribute to deoxyribonucleotide synthesis by means of both an NrdR and a Fur-dependent derepression of nrdHIEF due to hydrogen peroxide production and DNA damage associated with the oxidative burst, thus helping to overcome the host defenses
physiological function
P37146
the class Ib ribonucleotide reductase can initiate reduction of nucleotides to deoxynucleotides with either a MnIII 2-tyrosyl radical or a FeIII 2-tyrosyl radical cofactor in the NrdF subunit. Whereas FeIII 2-tyrosyl radical can self-assemble from FeII 2-NrdF and O2, activation of MnII 2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2
physiological function
Q81G56
the properties of tyrosyl radical metalloprotein NrdF loaded with iron or manganese are in general similar for interaction with catalyitc subunit NrdE and flavodoxin protein NrdI. The enzyme activity in presence of manganese is approximately an order of magnitude higher than that in presence of iron in the presence of the class specific physiological reductant NrdH
physiological function
P31350
a conserved cluster of charged residues, including Lys95, Glu98, Glu-05, and Glu174, at the interface may function as an ionic lock for small subunit M2 homodimer. The transfection of the wild-type small subunit M2 but not the K95E mutant rescues theG1/S phase cell cycle arrest and cell growth inhibition caused by the siRNA knockdown of M2
physiological function
-
the ribonucleotide reductase response to DNA damage does not operate similarly across the cell cycle at either the transcript or the protein level. Ribonucleotide reductase subunit mRNA levels are comparably low in both damaged and undamaged G1 cells and highly induced in damaged S/G2 cells. Transcript numbers becomes correlated with both protein levels and localization only upon DNA damage in a cell cycle-dependent manner. The differential ribonucleotide reductase response to DNA damage correlates with variable Mec1 kinase activity in the cell cycle in single cells. The transcription of ribonucleotide reductase genes is noisy and non-Poissonian in nature
physiological function
P39452
isoform NrdEF is induced during H2O2 stress. Induction is mediated by the inactivation of Fur, an iron-dependent repressor. NrdEF supports cell replication in iron-depleted cells. Iron binds to NrdF when it is expressed in iron-rich cells, but NrdEF is functional only in cells that are both iron-depleted and manganese-rich
physiological function
Q7LG56
in nontransformed cells only during quiescence, isoform p53R2 is required for maintenance of mitochondrial DNA and for optimal DNA repair after UV damage
physiological function
Bacillus anthracis ATCC 14579
-
the properties of tyrosyl radical metalloprotein NrdF loaded with iron or manganese are in general similar for interaction with catalyitc subunit NrdE and flavodoxin protein NrdI. The enzyme activity in presence of manganese is approximately an order of magnitude higher than that in presence of iron in the presence of the class specific physiological reductant NrdH
-
physiological function
Bacillus subtilis JH624
-
RNRs catalyze the conversion of nucleotides UDP, ADP, GDP, and CDP to deoxynucleotides, providing the monomeric building blocks required for DNA replication and repair
-
physiological function
Escherichia coli GR536
-
class Ib RNR converts nucleoside 5'-diphosphates to deoxynucleoside 5'-diphosphates in iron-limited and oxidative stress conditions
-
physiological function
Escherichia coli K-12 CM735
-
ribonucleoside diphosphate reductase is an essential enzyme for the biosynthesis of the four dNTP in all living cells
-
malfunction
Q5VRJ6, Q6K848
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
additional information
-
as the pH is elevated, the rate-determining step of RNR can be altered from a conformational change to proton-coupled electron transfer, and the altered driving force for F3Y oxidation, by residues adjacent to it in the pathway, is responsible for this change
additional information
-
RNR and the dNTP-synthesizing complex are closely linked to the replication proteins or replisome at the replication fork, coordinated organization of NrdB protein, and consequently RNR protein, with other replication proteins. NrdB is present in nucleoid-associated clusters during the replication period. These clusters disappear after replication ends. Replication hyperstructure model, overview
additional information
-
the reaction of class I RNRs involves tyrosyl or cysteinyl radicals and requires aerobic conditions, while for class II RNRs the reaction involves deoxyadenosyl or cysteinyl radicals and is independent of oxygen. The thiyl radical in class II RNR is believed to be generated directly at the active site using the cofactor 5'-deoxyadenosylcobalamin
additional information
-
the reaction of class Ia RNRs involves tyrosyl or cysteinyl radicals and requires aerobic conditions
additional information
-
the reaction of class I RNRs involves tyrosyl or cysteinyl radicals and requires aerobic conditions, while for class II RNRs the reaction involves deoxyadenosyl or cysteinyl radicals and is independent of oxygen
additional information
-
the reaction of class Ia RNRs involves tyrosyl or cysteinyl radicals and requires aerobic conditions
additional information
-
RNRs are allosterically regulated on two levels, overall activity and substrate specificity. The substrate specificity is regulated by the binding of dNTPs to the specificity site, ATP and dATP upregulate the reduction of CDP and UDP, whereas dTTP upregulates GDP reduction and dGTP increases the rate of ADP reduction. This regulation is essential to maintain balanced dNTP pools for DNA synthesis and repair. The overall activity is regulated by the binding of dATP (inhibition) or ATP (stimulation) to the socalled activity site in the ATP cone domain of the alpha2 subunit of RNRs from class Ia
additional information
-
RNRs are allosterically regulated on two levels, overall activity and substrate specificity. The substrate specificity is regulated by the binding of dNTPs to the specificity site, ATP and dATP upregulate the reduction of CDP and UDP, whereas dTTP upregulates GDP reduction and dGTP increases the rate of ADP reduction. This regulation is essential to maintain balanced dNTP pools for DNA synthesis and repair
additional information
-
RR is regulated transcriptionally and allosterically. RR activity is also controlled by subunit RR2 levels; structural basis for substrate selection, RR activity is lowest at high dATP concentrations when the hexamer population is high, egulation of RR by dATPinduced oligomerization, overview. RR is regulated transcriptionally and allosterically. RR is further regulated by subunit localization and by its protein inhibitor Sml1
additional information
-
transcriptional regulation of RNR classes as well as their differential function during infection of macrophage and epithelial cells, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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
P21524
-
-
-
?
ADP + reduced thioredoxin
2'-deoxy-ADP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ADP + reduced thioredoxin
2'-dADP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
benzimidazoleriboside diphosphate + reduced thioredoxin
2'-deoxybenzimidazolriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
CDP + dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
-
-
-
-
?
CDP + dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
P21524
-
-
-
?
CDP + dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
Bacillus subtilis JH624
-
-
-
-
?
CDP + reduced dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
-
-
-
-
?
CDP + reduced dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
-
-
-
-
?
CDP + reduced dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
P95484
-
-
-
?
CDP + reduced thioredoxin
2'-deoxy-CDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
CDP + reduced thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + reduced thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + reduced thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
coupled assay method with NADPH, transient spectrometric measurement of Y356 radical intermediate, Y356 radical initiation is prompted by excitation of a proximal anthraquinone or benzophenone chromophore on a 20-mer peptide Y-R2C19, bound to subunit alpha2, both the Anq and BPA-containing peptides are competent in deoxycytidine diphosphate formation and turnover occurs via Y731 to Y730 to C439 pathway-dependent radical transport in R1, overview. Peptide Y-R2C19 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
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
Leishmania donovani MHOM/IN/1983/AG83
-
-
-
-
?
CDP + thioredoxin
dCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin A
2'-dCDP + thioredoxin A disulfide + H2O
show the reaction diagram
Bacillus subtilis, Bacillus subtilis JH624
-
-
-
-
?
CDP + thioredoxin YosR
2'-dCDP + thioredoxin YosR disulfide + H2O
show the reaction diagram
Bacillus subtilis, Bacillus subtilis JH624
-
-
-
-
?
CTP + reduced thioredoxin
2'-dCTP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
dCDP + DTT disulifde + H2O
CDP + DTT
show the reaction diagram
Bacillus subtilis, Bacillus subtilis JH624
-
in the assays for the Fe- and Mn-loaded recombinant NrdF, a 10fold excess of recombinant NrdE is used, CDP is the substrate, ATP or dATP is the effector, and DTT is the reductant
-
-
r
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
O33839
-
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
-
class I RNRs
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
-
class Ia RNRs
-
-
?
nucleoside 5'-diphosphate + NrdH-redoxin
2'-deoxynucleoside 5'-diphosphate + NrdH-redoxin disulfide + H2O
show the reaction diagram
-
only class Ib RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class Ia RNRs
-
-
?
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 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-, the essential enzyme catalyzes the rate-limiting step in dNTP production for DNA synthesis
-
-
?
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
at the completion of each turnover cycle, the active site of R1 becomes oxidized and subsequently regenerates by a cysteine pair at its C-terminal domain R1-CTD, that acts in trans to reduce the active site of its neighboring monomer, R1-CTD interacts with the N-terminal domain of R1, R1-NTD, which involves a conserved two-residue sequence motif in the R1-NTD, overview
-
-
?
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
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
P69924
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
P11157
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
CDP, ADP and GDP are reduced very poorly in the absence of allosteric effectors
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
-
in the presence of in vivo concentrations of effectors and all 4 substrates 43% dCDP, 14% dUDP, 31% dADP and 12% dGDP are formed
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
maximal activity with E. coli thioredoxin
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
dithiothreitol at higher concentrations i.e. 100 mM can partially substitute for reduced T4 thioredoxin, the rate of CDP reduction is 10% of that obtained with the complete system
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
CDP is the only substrate that is reduced with a significant activity even in the absence of allosteric effectors
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
dithiothreitol serves as in vitro electron donor, maximal activity with 40 mM
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
dithiothreitol serves as in vitro electron donor, maximal activity with 50-75 mM
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
O69273
NrdH-redoxin obtained from an overproducing strain, no activity with E. coli thioredoxin
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus
-
high concentration of dithiothreitol serves as in vitro hydrogen donor, thioredoxin B of Scenedesmus obliqus and yeast thioredoxin are most effective donors
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
possible role in HSV-2-induced transformation
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
critical and rate-controlling step in pathway leading to DNA synthesis and cell replication
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus
-
thioredoxin is the physiological reductant
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
thioredoxin is the physiological reductant
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus, Mus musculus
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Escherichia coli overproducing
-
-
-
ir
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
the enzyme catalyses the rate-limiting step of DNA synthesis in the pathogen, classical pathway via tyrosyl radical
-
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
the catalytic reaction in class I RNR involves a long-range electron transfer, coupled to proton transfer, between the substrate binding site in protein R1 and the iron/radical site in protein R2
-
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
Leishmania donovani MHOM/IN/1983/AG83
-
the enzyme catalyses the rate-limiting step of DNA synthesis in the pathogen, classical pathway via tyrosyl radical
-
-
?
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
-
-
-
ir
UDP + reduced thioredoxin
2'-deoxy-UDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
-
-
UDP + reduced thioredoxin
2'-deoxy-UDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
-
-
UDP + reduced thioredoxin
2'-deoxy-UDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
-
-
GDP + thioredoxin
2'-deoxyGDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
DNA damage checkpoints modulate RNR activity through the temporal and spatial regulation of its subunits
-
-
-
additional information
?
-
-
each catalytic turnover by aerobic ribonucleotide reductase requires the assembly of the two proteins, R1 (alpha2) and R2 (beta2), to produce deoxyribonucleotides for DNA synthesis
-
-
-
additional information
?
-
-
no substrate activity for L-ribofuranosyl-adenine 5'-diphosphate
-
-
-
additional information
?
-
-
under normal conditions, the cell assembles stoichiometric amounts of tyrosyl radicals essential for enzyme activity per betabeta subunit dimer. Modulation of tyrosyl radical concentration is not involved in regulation of enzyme activity
-
-
-
additional information
?
-
-
the Sml1-R1 interaction causes SML1-dependent lethality, the CX2C motif of Rnr1 Is essential for viability. overview
-
-
-
additional information
?
-
-
mechanism of radical transport in the R1 subunit of the class I enzyme, overview
-
-
-
additional information
?
-
-
human p53R2 is a 351-residue p53-inducible ribonucleotide reductase small subunit, hp53R2 supplies dNTPs for DNA repair to cells in G0-G1 in a p53-dependent fashion, rather than exhibiting cyclic dNTP synthesis. Hp53R2 structure-function relationship determination and analysis, overview
-
-
-
additional information
?
-
O84835
ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides for DNA synthesis
-
-
-
additional information
?
-
-
ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides for DNA synthesis
-
-
-
additional information
?
-
-
ribonucleotide reduction is the unique step in DNA-precursor biosynthesis and involves radical-dependent redox chemistry and diverse metallo-cofactors, overview. The Mn-RNR from the Gram-positive bacterium Corynebacterium ammoniagenes, strain ATCC 6872, belongs a distinct RNR class IV enzyme
-
-
-
additional information
?
-
P50651, Q6Y657, Q9LSD0
RNR is an essential enzyme that provides dNTPs for DNA replication and repair, regulation in response to genotoxic stress, overview
-
-
-
additional information
?
-
-
CDP as substrate
-
-
-
additional information
?
-
-
CDP as substrate resulting information of product dCDP
-
-
-
additional information
?
-
-
dCDP is produced from CDP by the holoenzyme
-
-
-
additional information
?
-
-
peroxo-type intermediates occur in the non-heme di-iron enzyme class Ia ribonucleotide reductase. Water or a proton can bind to the di-iron site of ribonucleotide reductase and facilitate changes that affect the electronic structure of the iron sites and activate the site for further reaction. Two potential reaction pathways, spectroscopic and computational analysis, overview
-
-
-
additional information
?
-
-
ribonucleotide reductase catalyzes the reduction of ribonucleotides to deoxyribonucleotides. Electron transfer to and from the tyrosyl radical, at Y122, in RNR is coupled to a conformational change in the beta2 subunit, vibrational spectroscopy analysis, overview
-
-
-
additional information
?
-
-
substrate is CDP, R2 is the catalytic subunit
-
-
-
additional information
?
-
O84835
the RNR reaction involves replacement by hydrogen of the hydroxyl group on the 2'-carbon of the nucleoside diphosphate substrate. This chemically difficult replacement occurs by a free-radical mechanism. The enzyme employs a heterobinuclear MnIV/FeIII cluster for radical initiation. In essence, the MnIV ion of the cluster functionally replaces the Y radical of the conventional class I RNR. The Ct beta2 protein also autoactivates by reaction of its reduced MnII/FeII metal cluster with O2. In this reaction, an unprecedented MnIV/FeIV intermediate accumulates almost stoichiometrically and decays by one-electron reduction of the FeIV site. This reduction is mediated by the near-surface residue, Y222, overview
-
-
-
additional information
?
-
-
the RNR reaction involves replacement by hydrogen of the hydroxyl group on the 2'-carbon of the nucleoside diphosphate substrate. This chemically difficult replacement occurs by a free-radical mechanism. The enzyme employs a heterobinuclear MnIV/FeIII cluster for radical initiation. In essence, the MnIV ion of the cluster functionally replaces the Y radical of the conventional class I RNR. The Ct beta2 protein also autoactivates by reaction of its reduced MnII/FeII metal cluster with O2. In this reaction, an unprecedented MnIV/FeIV intermediate accumulates almost stoichiometrically and decays by one-electron reduction of the FeIV site. This reduction is mediated by the near-surface residue, Y222, overview
-
-
-
additional information
?
-
-
catalysis by a class I RNR begins when a cysteine residue in the alpha2 subunit is oxidized to a thiyl radical by a cofactor about 35 A away in the beta2 subunit. In a class Ia or Ib RNR, a stable tyrosyl radical is the C oxidant, whereas a MnIV/FeIII cluster serves this function in the class Ic enzyme from Chlamydia trachomatis
-
-
-
additional information
?
-
-
class Ia and Ib RNRs convert nucleoside diphosphates into 2'-deoxynucleoside diphosphates using glutaredoxin or thioredoxin as cofactor. Class II RNRs catalyze the same reaction but also convert nucleoside triphosphates to the correspondent 2'deoxy products, EC 1.17.4.2, overview
-
-
-
additional information
?
-
-
class Ia RNRs convert nucleoside diphosphates into 2'-deoxynucleoside diphosphates using glutaredoxin or thioredoxin as cofactor
-
-
-
additional information
?
-
-
the enzyme catalyzes the conversion of nucleoside 5'-diphosphates, NDPs, to deoxynucleotides, dNDPs. The active site for NDP reduction resides in the alpha2 subunit, and the essential diferric-tyrosyl radical, Y122 radical, cofactor that initiates transfer of the radical to the active site cysteine in R2 (C439), 35A removed, is located in subunit beta2. The oxidation involves a hopping mechanism through aromatic amino acids, Y122, W48, and Y356 in subunit beta2 to Y731, Y730, and C439 in subunit alpha2, and a reversible proton-coupled electron transfer
-
-
-
additional information
?
-
-
active-site structure and active-site model clusters, overview. Electron transfers and kinetic control, overview
-
-
-
additional information
?
-
-
C-terminus of one monomeric R1 subunit acts in trans to regenerate the active site of its neighboring monomer. The class I RNR active-site disulfide bridge between Cys225 and Cys462 must be reduced for a complete turnover. The electron required for this reduction is provided by a redox network, which involves a cysteine pair at the C-terminus of the R1 subunit, the thioredoxin or glutaredoxin system, and NADPH. For in vitro experiments, the disulfide bridge can be reduced by small thiol compounds such as DTT
-
-
-
additional information
?
-
-
in the class I RNRs, a tyrosine radical is generated in the beta2 subunit, a di-ironoxo enzyme. In class II a tyrosine radical is generated directly on alpha or alpha2 by cleavage of adenosylcobalamin. In both cases, the radical is channeled to a cysteine in the active site of the alpha subunit to initiate catalysis
-
-
-
additional information
?
-
-
in the presence of rNrdE, ATP, and CDP, Mn(III)2-Y* and Fe(III)2-Y* rNrdF generate dCDP at rates of 132 and 10 nmol min/mg, respectively
-
-
-
additional information
?
-
-
substrate is CDP with ATP as effector, detection of NH2Y radical intermediates capable of dNDP formation
-
-
-
additional information
?
-
-
the class I RNR active-site disulfide bridge between Cys225 and Cys462 must be reduced for a complete turnover. The electron required for this reduction is provided by a redox network, which involves a cysteine pair at the C-terminus of the R1 subunit, the thioredoxin or glutaredoxin system, and NADPH. For in vitro experiments, the disulfide bridge can be reduced by small thiol compounds such as DTT
-
-
-
additional information
?
-
-
the enzyme catalyzes the reduction of all four ribonucleotides to their corresponding deoxyribonucleotides, the R2 subunit contains a di-iron site, which generates a free radical by the reductive cleavage of molecular oxygen. The free radical is subsequently transferred to the R1 subunit, activating the nucleotide substrate for catalysis
-
-
-
additional information
?
-
-
Bacillus subtilis ribonucleotide reductase can be assayed as a holo-enzyme by using equivalent amounts of each subunit
-
-
-
additional information
?
-
Corynebacterium glutamicum R163
-
CDP as substrate
-
-
-
additional information
?
-
Bacillus subtilis JH624
-
in the presence of rNrdE, ATP, and CDP, Mn(III)2-Y* and Fe(III)2-Y* rNrdF generate dCDP at rates of 132 and 10 nmol min/mg, respectively
-
-
-
additional information
?
-
Bacillus subtilis JH624
-
Bacillus subtilis ribonucleotide reductase can be assayed as a holo-enzyme by using equivalent amounts of each subunit
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
Leishmania donovani, Leishmania donovani MHOM/IN/1983/AG83
-
-
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
-
class I RNRs
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
-
class Ia RNRs
-
-
?
nucleoside 5'-diphosphate + NrdH-redoxin
2'-deoxynucleoside 5'-diphosphate + NrdH-redoxin disulfide + H2O
show the reaction diagram
-
only class Ib RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class I and class II RNRs
-
-
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
class Ia RNRs
-
-
?
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
the essential enzyme catalyzes the rate-limiting step in dNTP production for DNA synthesis
-
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
possible role in HSV-2-induced transformation
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
critical and rate-controlling step in pathway leading to DNA synthesis and cell replication
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus
-
thioredoxin is the physiological reductant
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
thioredoxin is the physiological reductant
-
-
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Scenedesmus obliquus, Mus musculus
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
Herpes simplex virus
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ribonucleoside diphosphate + thioredoxin
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
Leishmania donovani, Leishmania donovani MHOM/IN/1983/AG83
-
the enzyme catalyses the rate-limiting step of DNA synthesis in the pathogen
-
-
?
GDP + thioredoxin
2'-deoxyGDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
DNA damage checkpoints modulate RNR activity through the temporal and spatial regulation of its subunits
-
-
-
additional information
?
-
-
each catalytic turnover by aerobic ribonucleotide reductase requires the assembly of the two proteins, R1 (alpha2) and R2 (beta2), to produce deoxyribonucleotides for DNA synthesis
-
-
-
additional information
?
-
-
the Sml1-R1 interaction causes SML1-dependent lethality, the CX2C motif of Rnr1 Is essential for viability. overview
-
-
-
additional information
?
-
-
human p53R2 is a 351-residue p53-inducible ribonucleotide reductase small subunit, hp53R2 supplies dNTPs for DNA repair to cells in G0-G1 in a p53-dependent fashion, rather than exhibiting cyclic dNTP synthesis. Hp53R2 structure-function relationship determination and analysis, overview
-
-
-
additional information
?
-
O84835
ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides for DNA synthesis
-
-
-
additional information
?
-
-
ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides for DNA synthesis
-
-
-
additional information
?
-
-
ribonucleotide reduction is the unique step in DNA-precursor biosynthesis and involves radical-dependent redox chemistry and diverse metallo-cofactors, overview. The Mn-RNR from the Gram-positive bacterium Corynebacterium ammoniagenes, strain ATCC 6872, belongs a distinct RNR class IV enzyme
-
-
-
additional information
?
-
P50651, Q6Y657, Q9LSD0
RNR is an essential enzyme that provides dNTPs for DNA replication and repair, regulation in response to genotoxic stress, overview
-
-
-
additional information
?
-
-
catalysis by a class I RNR begins when a cysteine residue in the alpha2 subunit is oxidized to a thiyl radical by a cofactor about 35 A away in the beta2 subunit. In a class Ia or Ib RNR, a stable tyrosyl radical is the C oxidant, whereas a MnIV/FeIII cluster serves this function in the class Ic enzyme from Chlamydia trachomatis
-
-
-
additional information
?
-
-
class Ia and Ib RNRs convert nucleoside diphosphates into 2'-deoxynucleoside diphosphates using glutaredoxin or thioredoxin as cofactor. Class II RNRs catalyze the same reaction but also convert nucleoside triphosphates to the correspondent 2'deoxy products, EC 1.17.4.2, overview
-
-
-
additional information
?
-
-
class Ia RNRs convert nucleoside diphosphates into 2'-deoxynucleoside diphosphates using glutaredoxin or thioredoxin as cofactor
-
-
-
additional information
?
-
-
the enzyme catalyzes the conversion of nucleoside 5'-diphosphates, NDPs, to deoxynucleotides, dNDPs. The active site for NDP reduction resides in the alpha2 subunit, and the essential diferric-tyrosyl radical, Y122 radical, cofactor that initiates transfer of the radical to the active site cysteine in R2 (C439), 35A removed, is located in subunit beta2. The oxidation involves a hopping mechanism through aromatic amino acids, Y122, W48, and Y356 in subunit beta2 to Y731, Y730, and C439 in subunit alpha2, and a reversible proton-coupled electron transfer
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5'-deoxyadenosylcobalamin
-
class II enzymes
adenosylcobalamin
P95484
absolutely requires adenosylcobalamin (as a radical generator) for activity, KM: 0.001 mM
diferric(III)-tyrosyl radical cofactor
-
FeIII2-tyrosyl radical cofactor
-
diferric(III)-tyrosyl radical cofactor
-
class I enzymes
-
dimanganese(III)-tyrosyl radical cofactor
-
the dimanganese(III)-tyrosyl radical cofactor, not the diferric-tyrosyl radical one, is the active metallocofactor in vivo
-
dimanganese(III)-tyrosyl radical cofactor
-
MnIII2-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
P37146
binding structure analysis with NrdF and NrdI, NrdF contributes to the electrostatic environment of the FMN binding pocket, overview
glutaredoxin
-
class Ia and Ib RNRs
glutaredoxin
-
class Ia RNRs
glutaredoxin
-
class Ia and Ib RNRs
glutaredoxin
-
class Ia RNRs
manganese-iron cofactor
-
the class Ic RNR from Chlamydia trachomatis uses a Mn(IV)/Fe(III) cofactor, with high specificity for MnIV, which functionally replaces the tyrosyl radical used by conventional class I RNRs to initiate substrate radical production. The intermediate decays by reduction of the Fe site to the active MnIV/FeIII-R2 complex. The reaction of the MnII/FeII-R2 species with H2O2 proceeds in three resolved steps: sequential oxidation to MnIII/FeIII-R2 and Mn(IV)/Fe(IV)-R2, followed by decay of the intermediate to the active Mn(IV)/Fe(III)-R2 product, kinetics and reaction mechanism, overview
manganese-iron cofactor
-
the class Ic RNR from Chlamydia trachomatis uses a MnIV/FeIII cofactor, with high specificity for MnIV in place of the tyrosyl radical for radical initiation, R2 is activated when its MnII/FeII form reacts with O2 to generate a MnIV/FeIV intermediate, which decays by reduction of the FeIV site to the active MnIV/FeIII state, the reduction step in this sequence is mediated by residue Y222, overview
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
O84835
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
-
NADPH
-
slight stimulation
NADPH
-
absolute requirement
T4 thioredoxin
-
absolute requirement; enzyme induced in E. coli by infection with bacteriophage T4
-
T4 thioredoxin
-
enzyme induced in E. coli by infection with bacteriophage T4
-
thioredoxin
-
-
thioredoxin
-
class Ia and Ib RNRs and class II RNRs
thioredoxin
-
class Ia RNRs
thioredoxin
-
class Ia and Ib RNRs and class II RNRs
thioredoxin
-
class Ia RNRs
MnIV/FeIII cofactor
-
electron transfer mechanism and conformational identification, role in reaction and mechanism, detailed overview
-
additional information
-
analysis of composition and conformation, and of the reaction mechanism of the metallo-cofactor, detailed overview
-
additional information
-
RNR is active with both FeIII2-tyrosyl radical and MnIII2-tyrosyl radical cofactors in the beta2 subunit, NrdF
-
additional information
-
cofactor specificity and binding, role in reaction, overview
-
additional information
-
metal cofactor composition and conformation analysis, complex stabilities and geometries, calculations and modelling of enzyme geometries including cofactors and active site, detailed overview
-
additional information
P37146
class Ib ribonucleotide reductase can initiate reduction of nucleotides to deoxynucleotides with either a MnIII 2-tyrosyl radical or a FeIII 2-tyrosyl radical cofactor in the NrdF subunit. Whereas FeIII 2-tyrosyl radical can self-assemble from FeII 2-NrdF and O2, activation of MnII 2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
activity depends on Ca2+
Co2+
-
class II enzymes contain cobalamin as cofactor
Fe
-
class I enzymes contain diferric(III)-tyrosyl radical cofactor
Fe2+
-
each beta-protomer of the small betabeta subunit (R2) contains a binuclear iron cluster with inequivalent binding sites: FeA and FeB. The majority of the protein binds only one Fe(II)atom per betabeta subunit. Additional iron occupation can be achieved upon exposure to O2 or in high glycerol buffers. The binding of the first Fe(II) atom to the active site in a beta-protomer (beta1) induces a global protein conformational change that inhibits access of metal to the active site in the other beta-protomer (betaII). The binding of the same Fe(II) atom also induces a local effect at the active site in beta1-protomer, which lowers the affinity for metal in the A-site
Fe2+
-
the manganese- and iron content of the R2 subunit decides about the enzyme activity, determination of metal contents, overview
Fe2+
-
classIb RNR biferrous site structure, the spectroscopically defined active site contains a 4-coordinate and a 5-coordinate Fe(II), weakly antiferromagnetically coupled via mu-1,3-carboxylate bridges, detailed spectral analysis, overview
Fe2+
O84835
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
Fe2+
-
assembly, maintenance, and role in catalysis of the Fe2 III/III-Y radical cofactor of Ecbeta2 subunit, structure modelling, detailed overview
Fe2+
-
monomers A and B exhibit mono- and binuclear iron occupancy, the active site iron coordination environment, involving E131, H134, D100, E194, E228, and H231, is different between monomers A and B, binding structure, overview. Mobility and accessibility of the radical iron center, and radical transfer pathway, overview
Fe2+
-
the enzyme contains only 0.06 mol iron per mol of R2F subunit
Fe2+
-
two Fe2+ ions, each bound to one histidine and one terminal acidic residue, with Asp84 binding to Fe1 and Glu204 binding to Fe2. The di-iron binding site is involved in the catalytic reaction and enzyme activation, overview
Fe2+
-
metal content determination of oxidized and reduced subunit R2, electronic features and nuclear geometry of the manganese and iron sites, kinetics, overview. 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. Structure modelling
Fe2+
-
the isolated recombinant NrdF contains a diferric-tyrosyl radical [Fe(III)2-Y.] cofactor
Fe2+
-
class Ia ribonucleotide reductase subunit R2 contains a diiron active site, active-site crystal structures of the Fe(II)Fe(II) and Fe(III)Fe(III) clusters, overview
Fe2+
P37146
class Ib ribonucleotide reductase can initiate reduction of nucleotides to deoxynucleotides with either a MnIII 2-tyrosyl radical or a FeIII 2-tyrosyl radical cofactor in the NrdF subunit. Whereas FeIII 2-tyrosyl radical can self-assemble from FeII 2-NrdF and O2, activation of MnII 2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2
Fe3+
-
-
Fe3+
-
MnIV/FeIII cofactor
Fe3+
-
diferric(III)-tyrosyl radical cofactor
Fe3+
-
class I enzymes contain diferric(III)-tyrosyl radical cofactor
Fe3+
-
class Ia ribonucleotide reductase subunit R2 contains a diiron active site, active-site crystal structures of the Fe(II)Fe(II) and Fe(III)Fe(III) clusters, overview
Iron
-
2.3 atoms of nonheme iron per molecule
Iron
-
subunit B2 contains iron, nonheme-like porphyrin complexes
Iron
-
B2 subunit contains 2 dinuclear Fe3+ centers; iron center is composed of 2 high spin iron atoms antiferromagnetically coupled through a micro-oxo bridge
Iron
-
2 iron atoms and a tyrosyl radical per 88000 Da subunit
Iron
-
B2 subunit contains 2 dinuclear Fe3+ centers
Iron
-
2 separate iron centers in subunit B2, 1 center on each beta subunit, distance between iron centers: 25 A, distance between Fe-Fe atoms: 3.3 A
Iron
-
X-ray absorption fine structure, EXAFS, of iron-containing subunit, Fe-Fe distance in subunit B2 is in the 3.26-3.48 A range
Iron
-
Fe2+ stimulates
Iron
-
iron binds directly to the enzyme structure and not via sulfur; iron center stabilizes tyrosyl radical, distance between the iron center and the tyrosyl radical is estimated to be 6-9.0 A
Iron
-
B2 subunit contains 2 nonidentical high spin Fe3+ ions in an antiferromagnetically coupled binuclear complex that resembles both methydroxohemerythrin and oxyhemerythrin
Iron
-
Raman spectroscopy of B2 subunit shows Fe-O vibration of an oxygen-coordinated ligand
Iron
-
oxo- or carboxylate-bridge between the antiferromagnetically coupled pair of high spin Fe3+, possibly with a binding oxo-group
Iron
-
120000 Da L2 subunit of regenerating liver contains iron
Iron
-
nonheme iron is an essential component of the enzyme
Iron
Chlorella pyrenoidosa, Scenedesmus obliquus
-
no stimulation by iron ions
Iron
-
1.8 mol of iron per mol of R2F subunit, dinuclear iron center
Iron
-
proposed in vitro mechanism for the assembly of the diferric tyrosyl radical cofactor of subunit R2
Iron
-
construction of heterobinuclear Mn(II)Fe(II) and Mn(III)Fe(III) clusters within a single beta-protomer of the small subunit of Escherichia coli ribonucleotide reductase due to differential binding affinity of the A- and B-sites. The binding of the first metal is under kinetic control. The binding of the first Fe(II) atom to the active site in a beta-protomer induces a global protein conformational change that inhibits access of metal to the active site in the other protomer and also induces a local effect at the active site in the first protomer, which lowers the affinity for metal in the A-site
Iron
-
iron is bound tightly to the protein. Enzyme activity is the same in presence and absence of EDTA
Iron
-
subunit R2 dimer has two equivalent dinuclear iron centers. Iron atoms have both histidine and carboxyl acid ligands and are bridged by the carboxylate group of E115
Iron
-
initiator of catalysis is the paramagnetic Fe(III)Fe(IV) state of the iron cluster. Proposition of reaction scheme of the iron site
Iron
-
the class Ic RNR from Chlamydia trachomatis uses a Mn(IV)/Fe(III) cofactor, with high specificity for Mn(IV) in place of the Y for radical initiation, R2 is activated when its MnII/FeII form reacts with O2 to generate a MnIV/FeIV intermediate, which decays by reduction of the FeIV site to the active Mn(IV)/Fe(III) state, the reduction step in this sequence is mediated by residue Y222, overview
Iron
-
may substitute or manganese
Manganese
-
construction of heterobinuclear Mn(II)Fe(II) and Mn(III)Fe(III) clusters within a single beta-protomer of the small subunit of Escherichia coli ribonucleotide reductase due to differential binding affinity of the A- and B-sites
Manganese
-
the class Ic RNR from Chlamydia trachomatis uses a Mn(IV)/Fe(III) cofactor, with high specificity for Mn(IV) in place of the Y for radical initiation, R2 is activated when its MnII/FeII form reacts with O2 to generate a MnIV/FeIV intermediate, which decays by reduction of the FeIV site to the active Mn(IV)/Fe(III) state, the reduction step in this sequence is mediated by residue Y222, overview
Manganese
-
dimanganic-tyrosyl radical cofactor
Mg2+
-
5-10 mM, 2-3fold stimulation, not required for enzyme activity
Mg2+
-
2fold stimulation
Mg2+
-
stimulates CDP but not ADP reduction
Mg2+
-
subunit B1 requires Mg2+ ions in the 10 mM concentration range for activity
Mg2+
-
absolutely required
Mg2+
-
thymus enzyme: about 50% activity in absence of added Mg2+, optimal Mg2+ concentration varies with concentration of nucleotide effector
Mg2+
-
2fold activation
Mg2+
-
-
Mg2+
-
activates
Mg2+
-
activates
Mg2+
-
class Ib ribonucleotide reductase is a dimanganese(III)-tyrosyl radical enzyme, with Tyr115. Subunit beta, NrdF, contains the metallo-cofactor, essential for the initiation of the reduction process
Mg2+
-
activates
Mn(IV)
-
MnIV/FeIII cofactor
Mn2+
O69273
EPR-silent Mn bound to the polypeptide chain, approx. 0.5 mol manganese ions/mol of R2F polypeptide
Mn2+
-
the manganese- and iron content of the R2 subunit decides about the enzyme activity, determination of metal contents, overview
Mn2+
-
R2F is a mangagnese-containing enzyme
Mn2+
O84835
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
Mn2+
-
0.8 mol manganese per mol of R2F subunit, oragnized in a coupled binuclear centre with paramagnetic ground state or in a weakly coupled binuclear centre with therminally populated paramagnetic excites state which appears as binuclear Mn2+, overview
Mn2+
-
metal content determination of oxidized and reduced subunit R2, electronic features and nuclear geometry of the manganese and iron sites, kinetics, overview. 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. Structure modelling
Mn2+
P37146
class Ib ribonucleotide reductase can initiate reduction of nucleotides to deoxynucleotides with either a MnIII 2-tyrosyl radical or a FeIII 2-tyrosyl radical cofactor in the NrdF subunit. Whereas FeIII 2-tyrosyl radical can self-assemble from FeII 2-NrdF and O2, activation of MnII 2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2. Structures of MnII 2-NrdF in complex with reduced and oxidized NrdI: a continuous channel connects the NrdI flavin cofactor to the NrdF MnII 2 active site.
Mn3+
-
the MnIII2-tyrosyl radical cofactor, not the diferric-tyrosyl radical one, is the active metallocofactor in vivo
Mn3+
-
dimanganese(III)-tyrosyl radical cofactor
additional information
-
Mg2+ is not required for activity in vitro
additional information
-
-
additional information
-
Mg2+ is not required for activity in vitro
additional information
-
model of enzyme regulation by nucleoside 5'-triphosphates
additional information
Herpes simplex virus
-
Mg2+ is not required for activity in vitro
additional information
-
salt-dependence of calf thymus enzyme: optimal activity in 40 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, pH 7.6, in the presence of 80-120 mM KCl, precipitation in lower salt concentration, inhibition in higher salt concentration
additional information
Chlorella pyrenoidosa, Scenedesmus obliquus
-
no stimulation by Mg2+ or Fe2+/Fe3+
additional information
-
the essential metallo-cofactor is a micro-oxo-micro-carboxylato-diiron cluster adjacent to a stable tyrosyl radical
additional information
-
enzyme redox states, overview
additional information
-
R2F does not contain the metals Fe, Co, Ni and Cu
additional information
-
Glu64 is found in the viral protein in the position that is usually occupied by a metal-coordinating aspartate in other R2s
additional information
-
active-site models for the intermediate X-Trp48 radical+ and X-Tyr122 radical, the active Fe(III)Fe(III)-Tyr122 radical, and the met Fe(III)Fe(III) states of Escherichia coli R2 are studied, using broken-symmetry density functional theory incorporated with the conductor-like screening solvation model, overview. Asp84 and Trp48 are most likely the main contributing residues to the result that the transient Fe(IV)Fe(IV) state is not observed in wild-type class Ia R2. Kinetic control of proton transfer to Tyr122 radical plays a critical role in preventing reduction from the active Fe(III)Fe(III)-Tyr122 radical state to the met state, which is potentially the reason why Tyr122 radical in the active state can be stable over a very long period
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(-)-epicatechin
-
interacts with the R2 protein, leading to a loss of the tyrosyl radical EPR signal. Proliferation of cells exposed to (-)-epicatechin is downregulated, and deoxyribonucleotide levels are significantly diminished
(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
Scenedesmus obliquus
-
0.2 mM, 50% inhibition
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
-
thymus enzyme, reversible inhibition
2'-Deoxy-2'-azidocytidine diphosphate
-
inactivation
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
-
0.009 mM, 50% inhibition, reversible
2,3,4-trihydroxybenzohydroxamic acid
-
0.012 mM, 50% inhibition, hydroxyurea-resistant cells
2,3,4-trihydroxybenzohydroxamic acid
-
0.0035 mM, 50% inhibition
2,3-Dihydro-1H-pyrazolo[2,3-a]imidazole
-
-
2,3-Dihydro-1H-pyrazolo[2,3-a]imidazole
-
mechanism of inhibition
2,3-Dihydro-1H-pyrazolo[2,3-a]imidazole
Herpes simplex virus
-
noncompetitive vs. CDP
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
-
0.01 mM, 50% inhibition
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
-
0.033 mM, 50% inhibition, reversible
3,4-dihydroxybenzohydroxamic acid
-
0.3 mM, 50% inhibition
3,4-dihydroxybenzohydroxamic acid
-
2.5 mM, 50% inhibition
3,4-dihydroxybenzohydroxamic acid
-
0.03 mM, 50% inhibition
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
-
2 mM, 41% inhibition, presence of 0.1 mM desferal potentiates inhibition; trivial name guanazole
3,5-diamino-1H-1,2,4-triazole
-
2.3 mM, 50% inhibition of CDP reduction, 2.6 mM, 50% inhibition of ADP reduction
3,5-diamino-1H-1,2,4-triazole
-
trivial name guanazole
3,5-diamino-1H-1,2,4-triazole
Herpes simplex virus
-
noncompetitive vs. CDP; trivial name guanazole
3,5-diamino-1H-1,2,4-triazole
-
0.001 mM, 50% inhibition of CDP and UDP reduction, 0.05 mM, 50% inhibition of ADP reduction
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
-
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
-
triapine
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-Methyl-5-amino isoquinoline-1-carboxaldehyde thiosemicarbazone
-
-
4-Methyl-5-amino isoquinoline-1-carboxaldehyde thiosemicarbazone
-
inhibits the non-heme iron subunit
4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone
-
; 0.0003 mM, 93% inhibition, 0.1 mM desferal reverses inhibition
4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone
-
-
4-Methyl-5-amino-1-formylisoquinoline thiosemicarbazone
Herpes simplex virus
-
inactivation, half-life: 3 min
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 5-sulfonate
-
no inhibition in the presence of excess iron
Acetohydroxamic acid
-
1 mM, 50% inhibition
Acetohydroxamic acid
-
-
ADP
Herpes simplex virus
-
competitive inhibition of CDP reduction
ATP
-
4 mM, 50% inhibition of GDP reduction in the presence of dTTP
ATP
-
CDP reduction is inhibited by free ATP
ATP
Herpes simplex virus
-
free ATP, 0.32 mM, 50% inhibition
ATP
Herpes simplex virus
-
3 mM, 65% inhibition
aurintricarboxylate
-
oligomeric form
aurintricarboxylate
Scenedesmus obliquus
-
0.005 mM, 50% inhibition; oligomeric form
bathophenanthroline disulfonate
-
-
bathophenanthroline sulfonate
-
5 mM, almost complete inhibition of CDP and GDP reduction
bathophenanthroline sulfonate
-
1.5 mM, complete inactivation after 30 min, complete reactivation with FeCl3
bathophenanthroline sulfonate
-
no effect in the presence of excess iron
benzohydroxamic acid
-
0.4 mM, 50% inhibition
butylphenyl-dGTP
-
0.13 mM, 50% inhibition of ADP reduction
Catechol derivatives
-
-
-
CDP
Herpes simplex virus
-
competitive inhibition of ADP reduction
CDP
-
competitive inhibition of UDP reduction
Cibacron blue F3 GA
-
-
cisplatin
-
more than 90% irreversible inhibition by inhibitor/enzyme ratios smaller than 2 under anaerobic conditions, 0.4 mM, 50% inhibition under aerobic conditions, inhibition of B1 subunit
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
-
Co2+
-
RNR activity chelates with copper leading to inactivation
dADP
-
product inhibition
dATP
-
0.0033 mM, 50% inhibition of CDP reduction, 0.0036 mM, 50% inhibition of GDP reduction; inhibition of CDP reduction
dATP
-
inhibition of ADP reduction; inhibition of CDP reduction; inhibition of GDP reduction; inhibition of UDP reduction
dATP
-
inhibition of ADP reduction; inhibition of CDP reduction; inhibition of GDP reduction; inhibition of UDP reduction
dATP
-
2.1 mM, 50% inhibition; inhibition of CDP reduction; weak inhibition of ADP reduction
dATP
-
inhibition of CDP reduction
dATP
-
inhibition of CDP, UDP, GDP and ADP reduction
dATP
Scenedesmus obliquus
-
-
dATP
-
inhibition of CDP reduction; inhibition of CDP, UDP, GDP and ADP reduction; noncompetitive inhibition vs. ADP, GDP and CDP
dATP
-
0.005 mM, 50% inhibition of CDP and UDP reduction, 0.005 mM, 50% inhibition of GDP and ADP reduction; inhibition of ADP reduction; inhibition of CDP reduction; inhibition of GDP reduction
dATP
-
inhibition of ADP reduction
dATP
-
inhibition of ADP reduction; inhibition of CDP reduction; inhibition of GDP reduction
dATP
-
inhibition of ADP reduction
dATP
-
inhibition of ADP reduction; inhibition of CDP reduction; inhibition of GDP reduction
dATP
-
inhibition of CDP reduction; inhibition of UDP reduction
dATP
-
inhibition of CDP and UDP reduction is reversed by ATP; inhibition of CDP reduction; inhibition of UDP reduction
dATP
-
0.1 mM, 96% inhibition of CDP reductase activity in dextran sulfate-treated cells, 85% inhibition of GDP reductase activity
dATP
Herpes simplex virus
-
HSV type 2, 1 mM, 20% inhibition
dATP
-
inhibition of CDP reduction
dATP
Scenedesmus obliquus
-
3.5 mM, 92% inhibition of activity in extracts; inhibition of CDP reduction
dATP
-
0.05 mM, 50% inhibition of CDP reduction in presence of optimum ATP concentration i.e. 6 mM, stimulation in absence of ATP; inhibition of CDP reduction
dATP
-
strong inhibition of the ATP activated enzyme, complete inhibition of GDP reduction, inhibition of ADP reduction
dATP
-
inhibition of CDP reduction in the presence of ATP
dATP
-
activation at low concentration with a KL1 value for specificity site binding of 0.0032 mM, inhibition at higher concentration with a KL2 value for activity site binding of 0.0173 mM
dATP
-
0.05 mM, 10% residual activity
dATP
-
dATP maximally stimulates CDP reduction at 8-10 microM followed by rapid inhibition at higher concentrations
dCDP
-
product inhibition
dCTP
-
1 mM, 50% inhibition of CDP reduction
dCTP
-
1.2 mM, 50% inhibition of CDP reduction, 0.89 mM, 50% inhibition of ADP reduction
deferoxamine mesylate
-
IC50 for subunit p53R2 is 0.00316 mM, IC50 for hRRM2 subunit is 0.5 mM
deferoxamine mesylate
-
an iron chelator
Desferrioxamine
-
-
dGDP
-
product inhibition
dGTP
-
0.08 mM, 50% inhibition of CDP reduction, 0.19 mM, 50% inhibition of GDP reduction; inhibition of CDP reduction
dGTP
-
inhibition of CDP reduction; inhibition of GDP reduction; inhibition of UDP reduction
dGTP
-
inhibition of ATP- and dATP stimulated CDP reduction
dGTP
-
1.2 mM, 50% inhibition of CDP reduction, 0.93 mM, 50% inhibition of ADP reduction
dGTP
-
inhibition of GDP reduction
dGTP
-
0.05 mM, 50% inhibition of GDP reduction; 0.1 mM, 50% inhibition of CDP and UDP reduction; inhibition of UDP reduction
dGTP
-
inhibition of UDP reduction
dGTP
-
0.1 mM, 12% residual activity
dithiothreitol
-
higher than 10 mM, activation below
dITP
-
inhibition of CDP reduction
dTTP
-
0.2 mM, 50% inhibition of CDP reduction
dTTP
-
inhibition of CDP reduction; inhibition of UDP reduction
dTTP
-
inhibition of CDP reduction
dTTP
-
inhibition of CDP reduction
dTTP
-
inhibition of ADP- CDP- and UDP reduction
dTTP
-
inhibition of UDP reduction
dTTP
-
inhibition of ADP reduction
dTTP
-
inhibition of UDP reduction
dTTP
Herpes simplex virus
-
HSV type 2, 1 mM, 20% inhibition
dTTP
Chlorella pyrenoidosa, Scenedesmus obliquus
-
inhibition of CDP reduction
dUDP
-
product inhibition
dUTP
-
inhibition of: CDP reduction, UDP reduction
EDTA
-
reversible stimulation of GDP reduction, irreversible inhibition of CDP reduction
EDTA
Mus musculus, Scenedesmus obliquus
-
-
EDTA
-
1 mM, 72% inhibition
EDTA
Scenedesmus obliquus
-
10 mM, 50% inhibition
ethyleneglycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid
-
trivial name EGTA
Fe2+
Scenedesmus obliquus
-
concentrations higher than 0.1-1 mM
Fe2+
Scenedesmus obliquus
-
0.2 mM, 50% inhibition
Fe2+
-
no effect of iron salts
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
-
i.e. F2dNDP, inhibitor forming a furanone intermediate. Modeling of enzyme-inhibitor complex
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
-
1 mM, 98 and 81% inhibition of CDP and GDP reduction respectively
Hydroxyurea
-
0.025 mM, 50% inhibition
Hydroxyurea
-
10 mM, complete inhibition, 0.3 mM, 50% inhibition
Hydroxyurea
-
0.5 mM, 50% inhibition
Hydroxyurea
-
2 mM, 93% inhibition, presence of 0.1 mM desferal potentiates inhibition
Hydroxyurea
-
1 mM, complete inactivation of thymus enzyme
Hydroxyurea
Saccharomyces cerevisiae, Scenedesmus obliquus
-
-
Hydroxyurea
-
inhibits the non-heme iron subunit; mechanism of inhibition
Hydroxyurea
-
-
Hydroxyurea
Scenedesmus obliquus
-
1.5 mM, 50% inhibition
Hydroxyurea
-
-
Hydroxyurea
-
0.01-0.03 mM, 50% inhibition, 0.2 mM, complete inhibition
Hydroxyurea
-
1 mM, approx. 90% inhibition; thymus enzyme, reversible inhibition
Hydroxyurea
-
approx. 0.5 mM, 50% inhibition
Hydroxyurea
O69273
2 mM, approx. 80% inactivation
Hydroxyurea
-
IC50 for subunit p53R2 is 2.48 mM, IC50 for hRRM2 subunit is 0.991 mM
Hydroxyurea
-
inhibition of the enzyme by the 1-electron donor hydroxyurea produces the Mn(III)Fe(III) state
Hydroxyurea
-
inhibits the M2 subunit
Hydroxyurea
-
-
Hydroxyurea
Q5VRJ6, Q6K848
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; 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
Hydroxyurea
-
inactivates both Ia/b and Ic beta2 subunits by reducing their C oxidants, reacts with the MnIV/FeIII cofactor to give two distinct products: the homogeneous MnIII/FeIII-beta2 complex, which forms only under turnover conditions, in the presence of alpha2 and the substrate, and a distinct, diamagnetic Mn/Fe cluster, which forms about 900fold less rapidly as a second phase in the reaction under turnover conditions and as the sole outcome in the reaction of MnIV/FeIII-beta2 only
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
-
-
Mg2+
-
1-5 mM, 10-20% inhibition of GDP reduction; inhibition of CDP reduction
Mg2+
-
uncomplexed Mg2+
Mg2+
Herpes simplex virus
-
uncomplexed Mg2+, 3.7 mM, 50% inhibition
Mg2+
Scenedesmus obliquus
-
2 mM, 50% inhibition
Mn2+
Scenedesmus obliquus
-
concentrations higher than 0.1-1 mM
Mn2+
Scenedesmus obliquus
-
0.2 mM, 50% inhibition
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
Scenedesmus obliquus
-
5 mM, 50% inhibition
N-Hydroxy-alpha-aminohexanoate
Scenedesmus obliquus
-
15 mM, 50% inhibition
N-hydroxyguanidine
-
10 mM, 89% inhibition
N-hydroxyurethane
-
10 mM, 66% inhibition
N-Methyl 3,4,5-trihydroxybenzamide
-
-
N-Methylhydroxylamine
-
10 mM, 94% inhibition
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
-
-
N6-(3-pyrazolyl)-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
-
-
N6-cyclobutyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
-
-
N6-cycloheptyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
-
-
N6-endo-norbonyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
-
-
N6-phenyl-9H-(3-C-methyl-beta-D-ribofuranosyl)adenine
-
-
nicotinohydroxamic acid
-
0.8 mM, 50% inhibition
NSFTLDADF
-
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
-
overview
-
o-ClBzocFc[ELDK]DF
-
inhibitor identified by competition with inhibitor N-AcFTLDADF and inhibition of enzyme activity
p-chloromercuribenzoate
-
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
-
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
-
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
-
Periodate-oxidized inosine
-
-
-
Periodate-oxidized inosine
Herpes simplex virus
-
inactivation, 1 mM, half-life: 6 min
-
phenylacetohydroxamic acid
-
1 mM, 50% inhibition
picolinohydroxamic acid
-
0.5 mM, 50% inhibition
Polyhydroxybenzohydroxamic acid
-
-
-
pyrazoloimidazol
-
2 mM, 79% inhibition, presence of 0.1 mM desferal potentiates inhibition, inhibits the non-heme iron subunit
pyrazoloimidazol
-
-
Pyridine-2-carboxaldehyde thiosemicarbazone
-
-
pyridoxal 5'-phosphate
Herpes simplex virus
-
1 mM, 65% inhibition, 3 mM, 90% inhibition
pyridoxal 5'-phosphate/NaBH4
-
-
Pyrogallol derivatives
-
-
-
quercetin
-
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
-
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
-
Sml1 protein
-
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
-
Sodium arsenite
-
0.025 mM, almost complete inhibition of CDP reduction, 86% inhibition of GDP reduction
Synthetic peptides
-
which specifically inhibit the activity of virus-induced enzyme
-
Thenoyltrifluoroacetone
-
5 mM, almost complete inhibition of CDP and GDP reduction
Thenoyltrifluoroacetone
-
-
triapine
-
IC50 for subunit p53R2 is 112 nM, IC50 for hRRM2 subunit is 144 nM
triapine
-
i.e. 3-AP, triapine enhances the cytotoxicity of gemcitabine and arabinoside cytosine in four non-small-cell-lung-cancer cell lines, e.g. in SW1573 cells, but not in H460 cells, multiple-drug-effect analysis, overview
UDP
-
competitive inhibition of CDP reduction
UDP
-
inhibition of CDP reduction
YAGAVVNDL
Herpes simplex virus
-
peptide may prevent association of the two subunits by competing for the subunit binding site
YGAVVNDL
Herpes simplex virus
-
-
-
[bis(2-acetylpyridine N,N-dimethylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
-
-
[bis(2-acetylpyridine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
-
-
[bis(2-acetylpyridine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
-
-
[bis(2-acetylpyridine N-pyrrolidinylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
-
-
[bis(2-acetylpyridine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
-
-
[bis(2-acetylpyridine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
-
-
[bis(acetylpyrazine N,N-dimethylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
-
-
[bis(acetylpyrazine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
-
-
[bis(acetylpyrazine N,N-dimethylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
-
-
[bis(acetylpyrazine N-piperidinylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
-
-
[bis(acetylpyrazine N-piperidinylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
-
-
[bis(acetylpyrazine N-piperidinylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
-
-
[bis(acetylpyrazine N-pyrrolidinylthiosemicarbazonato)-N,N,S-gallium(III)] hexafluorophosphate
-
-
[bis(acetylpyrazine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] hexafluorophosphate
-
-
[bis(acetylpyrazine N-pyrrolidinylthiosemicarbazonato)-N,N,S-iron(III)] tetrachloroferrate(III)
-
-
[FeCl4] 2-acetylpyridine N,N-dimethylthiosemicarbazone
-
Ga(III) and Fe(III) complexes destroy the tyrosyl radical of the presumed target ribonucleotide reductase
[FeCl4] 2-acetylpyridine N-pyrrolidinylthiosemicarbazone
-
-
[FeCl4] acetylpyrazine N,N-dimethylthiosemicarbazone
-
-
[FeCl4] acetylpyrazine N-piperidinylthiosemicarbazone
-
-
[FeCl4] acetylpyrazine N-pyrrolidinylthiosemicarbazone
-
-
[GalCl2] 2-acetylpyridine N,N-dimethylthiosemicarbazone
-
Ga(III) and Fe(III) complexes destroy the tyrosyl radical of the presumed target ribonucleotide reductase
[GalCl2] 2-acetylpyridine N-pyrrolidinylthiosemicarbazone
-
-
[GalCl2] acetylpyrazine N,N-dimethylthiosemicarbazone
-
-
[GalCl2] acetylpyrazine N-piperidinylthiosemicarbazone
-
-
[GalCl2] acetylpyrazine N-pyrrolidinylthiosemicarbazone
-
-
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
-
additional information
Herpes simplex virus
-
enzyme does not respond to feedbck inhibition by dTTP or dATP
-
additional information
-
inhibition of reductase by hydroxyurea, guanazole and pyrazolo-imidazole is potentiated by iron-chelating agents e.g. EDTA, desferrioxamine mesylate and 8-hydroxyquinoline, inhibition by 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone and 1-formylisoquinoline thiosemicarbazone is reversed by iron chelating agents
-
additional information
-
each ribonucleoside diphosphate substrate is competitively inhibited by reduction of each other substrate
-
additional information
-
overview: naturally occuring inhibitors e.g. proteins and nucleotides
-
additional information
-
-
-
additional information
-
overview: naturally occuring inhibitors e.g. proteins and nucleotides
-
additional information
Herpes simplex virus
-
mechanism studied with inhibitors
-
additional information
-
L1210 cells with resistance to specific nucleotide reductase inhibitors
-
additional information
-
overview
-
additional information
-
-
-
additional information
-
mechanism-based inhibitors
-
additional information
Herpes simplex virus
-
-
-
additional information
-
not inibited by 8-hydroxyquinoline and o-phenanthroline
-
additional information
Herpes simplex virus
-
not inhibited by dATP and dTTP
-
additional information
-
comprehensive and quantitative model for allosteric control of mRR enzymatic activity based on molecular mass, ligand binding and enzyme activity studies
-
additional information
-
8-vinyl-ADP is efficiently reduced. The anti-tumoral and anti-viral activity of 8-vinyladenosine can unlikely result from inhibition of ribonucleotide diphosphate reductase
-
additional information
-
not inhibitory: EDTA
-
additional information
-
reaction involves formation of a keto-deoxyribonucleotide intermediate. In case of furanone inhibitors, the intermediate dissociates from the active site, depending on the solvation free energy of the 2-substituents, its influence inside the active site, and the charge transfer mechanism from a protein side chain to solution as thermodynamic driving forces. Substrates do not dissociate from the active site but complete the catalytic cycle
-
additional information
-
no enzyme inhibition by arabinoside cytosine
-
additional information
-
synthesis, characterization, cytotoxicity in human cell lines, and interaction with ribonucleotide reductase of gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones, overview, gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands
-
additional information
-
synthesis, characterization, and interaction with ribonucleotide reductase subunit R2 of gallium(III) and iron(III) complexes of alpha-N-heterocyclic thiosemicarbazones, overview, gallium(III) enhances, whereas iron(III) weakens the cytotoxicity of the ligands
-
additional information
-
construction and synthesis of ribose-modified purine nucleosides as ribonucleotide reductase inhibitors. Synthesis, antitumor activity, and molecular modeling of N6-substituted 3-C-methyladenosine derivatives, an unsubstituted N6-amino group is essential for optimal cytotoxicity of 3'-Me-Ado. The anticancer nucleosides act as antimetabolites after metabolic activation by phosphorylation to the corresponding 5'-di- or 5'-triphosphates, overview
-
additional information
-
synthesis and evaluation of peptide inhibitors of RNR derived from the C-terminus of the small subunit of Mycobacterium tuberculosis RNR, based on the heptapeptide Ac-Glu-Asp-Asp-Asp-Trp-Asp-Phe-OH with Trp5 and Phe7 being very important for inhibitory potency, overview
-
additional information
-
inhibitory mechanisms of heterocyclic carboxaldehyde thiosemicabazones
-
additional information
-
synthesis and ribonucleotide reductase inhibitory activity of thiosemicarbazones, overview
-
additional information
-
the enzyme is inhibited by radical scavengers
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
25 mM, maximal activation, 70% of activity with dithiothreitol
adenyl-5'-yl-imidodiphosphate
-
maximal activation of CDP reduction at 4 mM
adenyl-5'-yl-imidodiphosphate
-
can replace ATP as activator of CDP and UDP reduction
adenyl-5'-yl-imidodiphosphate
-
stimulation at low concentration, inhibition above 0.3 mM
ATP
-
reduction of CDP is dependent on ATP or adenyl-5'-yl iminodiphosphate
ATP
-
further stimulation of dTTP activated GDP reduction; reduction of CDP and UDP requires 1-2 mM ATP
ATP
-
stimulation of CDP reduction
ATP
-
stimulation of ADP reduction; stimulation of CDP reduction
ATP
-
stimulation of CDP reduction; stimulation of UDP reduction
ATP
-
stimulation of CDP reduction; stimulation of UDP reduction
ATP
-
stimulation of CDP reduction; stimulation of UDP reduction
ATP
-
stimulation of CDP reduction
ATP
-
stimulation of CDP reduction; stimulation of UDP reduction
ATP
-
stimulation of CDP reduction
ATP
-
stimulation of CDP reduction
ATP
Scenedesmus obliquus
-
stimulation of CDP reduction
ATP
-
most effective activator
ATP
O69273
stimulation of CDP reduction
ATP
-
required for CDP reduction
ATP
-
ATP is an allosteric effector
ATP
-
stimulates the reduction of CDP and ADP
ATP
-
ATP maximally stimulates CDP reduction at 1.5 mM
dATP
-
stimulation of GDP reduction
dATP
-
stimulation of CDP and UDP reduction
dATP
-
stimulation of CDP and UDP reduction
dATP
-
0.005 mM, stimulation of CDP reduction in absence of ATP, inhibition in presence of ATP
dATP
-
strong stimulation of CDP reduction
dATP
O69273
stimulation of CDP reduction
dATP
-
6fold stimulation of GDP reduction; stimulation of ADP reduction
dATP
-
0.2-0.4 mM, induces formation of dimers and tetramers of subunit R1, 1-2 mM, induces formation of hexamers of subunit R1
dATP
-
activation at low concentration with a KL1 value for specificity site binding of 0.0032 mM, inhibition at higher concentration with a KL2 value for activity site binding of 0.0173 mM
dATP
-
positive effector
dATP
-
activates
dATP
-
dATP maximally stimulates CDP reduction at 8-10 microM followed by rapid inhibition at higher concentrations
dCTP
-
stimulation of CDP reduction
dCTP
-
stimulation of UDP reduction
dCTP
-
stimulation of CDP and ADP reduction
dGDP
-
40% less effective than dGTP
dGTP
-
required for ADP reduction, maximal activity with 0.01 mM dGTP
dGTP
-
stimulation of ADP reduction
dGTP
-
stimulation of ADP reduction; stimulation of GDP reduction
dGTP
-
stimulation of ADP reduction; stimulation of tubercidin diphosphate reduction
dGTP
-
stimulation of tubercidin diphosphate reduction
dGTP
-
stimulation of ADP reduction; stimulation of tubercidin diphosphate reduction
dGTP
-
stimulation of tubercidin diphosphate reduction
dGTP
-
stimulation of ADP reduction; stimulation of tubercidin diphosphate reduction
dGTP
-
stimulation of tubercidin diphosphate reduction
dGTP
-
stimulation of CDP reduction
dGTP
-
activation of ADP reduction
dGTP
-
stimulation of ADP reduction
dGTP
-
stimulation of ADP reduction
dGTP
-
slight stimulation of CDP reduction
dGTP
-
required for ADP reduction
dGTP
-
stimulates the reduction of CDP and ADP
Dihydrolipoic acid
-
slight stimulation
dithioerythritol
-
0.5 mM, maximal activation, 94% of activity with dithiothreitol
Dithiols
-
required for in vitro reduction
-
Dithiols
Scenedesmus obliquus
-
required for reduction of CDP in vitro
-
dithiothreitol
-
slight activation
dithiothreitol
-
required for optimal activity
dithiothreitol
Scenedesmus obliquus
-
high concentrations serve as in vitro hydrogen donor
dithiothreitol
-
optimal in vitro activity with 10 mM, inhibition above
dITP
-
activation of ADP reduction
DTT
-
required for activity
dTTP
-
stimulation of GDP reduction
dTTP
-
absolutely required for GDP reduction, less than 10% activity in the absence of dTTP, maximal stimulation with 0.001-0.1 mM dTTP in the absence of ATP and 0.1-1 mM in the presence of ATP, inhibition above; required for ADP reduction; stimulation of GDP reduction
dTTP
-
stimulation of ADP reduction; stimulation of CDP reduction; stimulation of GDP reduction; stimulation of UDP reduction
dTTP
-
stimulation of 2,6-diaminopurine riboside reduction; stimulation of 2-aminopurineriboside diphosphate reduction; stimulation of benzimidazoleriboside diphosphate reduction; stimulation of CDP reduction; stimulation of GDP reduction; stimulation of purine riboside diphosphate reduction; stimulation of UDP reduction
dTTP
Saccharomyces cerevisiae, Scenedesmus obliquus
-
stimulation of 2,6-diaminopurine riboside reduction; stimulation of 2-aminopurineriboside diphosphate reduction; stimulation of benzimidazoleriboside diphosphate reduction; stimulation of CDP reduction; stimulation of purine riboside diphosphate reduction; stimulation of UDP reduction
dTTP
-
stimulation of GDP reduction
dTTP
-
stimulation of GDP reduction
dTTP
-
stimulation of CDP reduction; stimulation of UDP reduction
dTTP
-
slight stimulation of CDP reduction
dTTP
O69273
stimulation of CDP reduction
dTTP
-
required for GDP reduction
E. coli thioredoxin reductase
-
absolute requirement; enzyme induced in Escherichia coli by infection with bacteriophage T4
-
EDTA
-
reversible stimulation of GDP reduction, irreversible inhibition of CDP reduction
GTP
-
stimulation of CDP and ADP reduction
NrdI
-
is an essential player in Escherichia coli class Ib RNR cluster assembly, overview. Preparation of recombinant N-terminally His6-tagged NrdI
-
NrdI
P37146
involved in binding of FMN. Whereas FeIII 2-tyrosyl radical can self-assemble from FeII 2-NrdF and O2, activation of MnII 2-NrdF requires a reduced flavoprotein, NrdI, proposed to form the oxidant for cofactor assembly by reduction of O2. Lys260 is involved in a hydrogen bond network with the strictly conserved residues Tyr256 and NrdI Glu110, mechanism of MnII 2-NrdF activation by NrdIhq and O2, overview
-
O2
-
activates the MnIV/FeIII cofactor, overview
P1,P5-di(adenosine 5')tetraphosphate
-
stimulation at low concentrations, inhibition above 0.3 mM
-
P53
-
activates, required
phosphate
Scenedesmus obliquus
-
up to 50 mM, pH 6.7: necessary for activity, decrease of activity at higher values
phosphate
-
50 mM, slight stimulation, inhibition at 200 mM
thioredoxin reductase
-
Escherichia coli enzyme
-
H2O2
-
activation
additional information
-
enzyme of cells first treated with 2,6-dichlorophenolindophenol has a complete dependence on NADPH which can also be met by dithiothreitol or dihydrolipoic acid
-
additional information
-
ribonucleoside effectors are exclusively bound at effector binding sites on subunit B1 controlling substrate specificity and activity
-
additional information
-
overview: stimulation of various enzymes; stimulation by effector nucleotides; stimulation with various substrates
-
additional information
-
stimulation by effector nucleotides
-
additional information
Scenedesmus obliquus
-
stimulation by effector nucleotides; stimulation with various substrates
-
additional information
-
overview: nucleoside 5'-diphosphates as effectors of mammalian ribonucleotide reductase
-
additional information
-
subunit R1 has 2 effector-binding sites per polypeptide chain: one activity site for dATP and ATP, with dATP-inhibiting and ATP-stimulating catalytic activity and a second specificity site for dATP, ATP, dTTP and dGTP directing substrate specificity
-
additional information
-
comprehensive and quantitative model for allosteric control of mRR enzymatic activity based on molecular mass, ligand binding and enzyme activity studies
-
additional information
-
quantitative activation
-
additional information
-
enzyme activation mechanism and kinetics, overview
-
additional information
-
mechanism for the activation of peroxy intermediates in binuclear non-heme iron enzymes for reactivity
-
additional information
-
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
-
additional information
-
TTP, dATP, TTP/GDP, TTP/ATP, and TTP/dATP, 1. TTP bound at the S-site, 2. dATP bound at the S-site, 3. TTP bound at the S-site and GDP at the C-site, 4. TTP bound at the S-site and ATP at the A-site, and 5. TTP bound at the S-site and dATP at the A-site
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0078
-
ADP
Herpes simplex virus
-
-
0.048
-
ADP
-
in the presence of 0.007 mM dGTP as effector
0.095
-
ADP
-
optimum dGTP concentration
0.2
-
ADP
-
in the presence of 0.2 mM GTP
0.07
-
ATP
-
positive effector of CDP reduction
0.00049
-
CDP
Herpes simplex virus
-
-
0.0014
-
CDP
-
in the presence of 5'-adenylimidodiphosphate
0.0023
-
CDP
-
in the presence of ATP
0.021
-
CDP
-
in the presence of 1.5 mM ATP
0.033
-
CDP
-
in the presence of 3.6 mM dCTP
0.043
-
CDP
-
in the presence of 0.002 mM dATP as effector
0.05
-
CDP
-
-
0.056
-
CDP
-
in the presence of 0.5 mM ATP as effector
0.057
-
CDP
-
in the presence of 0.02 mM dTTP as effector
0.09
-
CDP
-
subunit L1
0.003
-
dATP
-
positive effector of CDP reduction
0.0015
-
dTTP
-
positive effector of CDP reduction
0.04
-
GDP
-
in the presence of 0.4 mM dTTP as effector
0.24
-
GDP
-
-
0.00013
-
glutaredoxin
-
-
0.003
-
thioredoxin
-
-
0.1
-
UDP
-
in the presence of 0.3 mM ATP as effector
additional information
-
additional information
-
effect of different nucleoside triphosphates on Km
-
additional information
-
additional information
-
effect of different nucleoside triphosphates on Km
-
additional information
-
additional information
-
kinetics, overview
-
additional information
-
additional information
-
enzyme redox states, overview
-
additional information
-
additional information
-
pre-steady state kinetics, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.047
-
CDP
-
CDP reduction in the absence of allosteric effectors
0.16
-
CDP
-
CDP reduction in the presence of 1 mM ATP
0.26
-
CDP
-
CDP reduction in the presence of 0.2 mM ATP
0.29
-
CDP
-
CDP reduction in the presence of 4 mM ATP
3.33
-
CDP
-
activity of subunit B1 assayed in the presence of an excess of subunit B2
12.9
-
CDP
-
activity of subunit B2 assayed in the presence of an excess of subunit B1
additional information
-
additional information
-
turnover number of wild-type and mutant proteins of R1 protein
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.023
-
2'-Deoxy-2'-azidocytidine diphosphate
-
-
0.0037
-
2'-methyladenosine 5'-diphosphate
-
vs. ADP
0.0079
-
2'-methyladenosine 5'-diphosphate
-
vs. GDP
0.084
-
2'-methyluridine 5'-diphosphate
-
vs. UDP
0.115
-
2'-methyluridine 5'-diphosphate
-
vs. CDP
1.1
-
2,3-Dihydro-1H-pyrazolo[2,3-a]imidazole
Herpes simplex virus
-
derived from slope
1.5
-
2,3-Dihydro-1H-pyrazolo[2,3-a]imidazole
Herpes simplex virus
-
derived from intercept
0.0055
-
ADP
-
vs. GDP
0.011
-
ADP
Herpes simplex virus
-
competitive inhibition of CDP reduction
0.014
-
ADP
-
vs. CDP
0.036
-
ADP
-
vs. UDP
0.00042
-
CDP
Herpes simplex virus
-
competitive inhibition of ADP reduction
0.00058
-
CDP
-
vs. GDP
0.0007
-
CDP
-
vs. ADP
0.0019
-
CDP
-
vs. UDP
0.00004
-
clofarabine
-
pH not specified in the publication, temperature not specified in the publication
0.0002
-
dATP
-
in the presence of 0.15 mM dGTP
0.0004
-
dATP
-
in the presence of 0.55 mM dTTP
0.0005
-
dATP
-
in the presence of 0.005 mM dGTP
0.0006
-
dATP
-
in the presence of 0.05 mM dTTP
0.0004
-
dGTP
-
with 0.001 mM dATP as positive effector
0.0005
-
dGTP
-
with 0.02 mM dATP as positive effector
0.0009
-
dGTP
-
with 0.17 mM ATP as positive effector
0.0018
-
dGTP
-
with 1.7 mM ATP as positive effector
0.0006
-
GDP
-
vs. ADP
0.0012
-
GDP
-
vs. CDP
0.0018
-
GDP
-
vs. UDP
0.007
-
GDP
-
competitive vs. CDP
14
-
guanozole
Herpes simplex virus
-
derived from intercept
27
-
guanozole
Herpes simplex virus
-
derived from slope
0.69
-
Hydroxyurea
-
-
0.02
-
N-alpha-acetyl-FTLDADF
-
N-alpha-acetyl heptapeptide, identical to the last seven amino acids of R2 subunit C-terminus from mouse enzyme
0.0058
-
UDP
-
vs. GDP
0.042
-
UDP
-
vs. CDP
0.043
-
UDP
-
vs. ADP
0.5
-
UDP
-
competitive vs. CDP
1
-
L-ADP
-
-
additional information
-
additional information
-
inhibition kinetics of clofarabine di- and triphosphates, overview
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.011
-
(2E)-2-(anthracen-9-ylmethylidene)-N-hydroxyhydrazinecarboximidamide
-
pH not specified in the publication, temperature not specified in the publication
0.5
-
2-furan-3-ylbenzaldehyde N-(4-hydroxyphenyl)thiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
2-furan-3-ylbenzaldehyde N-phenylthiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
2-hydroxybenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
2-hydroxybenzaldehyde N-phenylthiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
2-thiophen-2-ylbenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
2-thiophen-2-ylbenzaldehyde N-phenylthiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
4-hydroxy-3-methoxybenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
above, pH 7.2, 37C
0.5
-
4-hydroxy-3-methoxybenzaldehyde N-phenylthiosemicarbazone
-
above, pH 7.2, 37C
0.047
-
4-hydroxybenzaldehyde N-(2-chlorophenyl)thiosemicarbazone
-
pH 7.2, 37C
0.029
-
4-hydroxybenzaldehyde N-(2-hydroxyphenyl)thiosemicarbazone
-
pH 7.2, 37C
0.042
-
4-hydroxybenzaldehyde N-(2-methoxyphenyl)thiosemicarbazone
-
above, pH 7.2, 37C
0.037
-
4-hydroxybenzaldehyde N-(2-methylphenyl)thiosemicarbazone
-
pH 7.2, 37C
0.039
-
4-hydroxybenzaldehyde N-(2-nitrophenyl)thiosemicarbazone
-
pH 7.2, 37C
0.029
-
4-hydroxybenzaldehyde N-(3-chlorophenyl)thiosemicarbazone
-
pH 7.2, 37C
0.029
-
4-hydroxybenzaldehyde N-(3-hydroxyphenyl)thiosemicarbazone
-
pH 7.2, 37C
0.03
-
4-hydroxybenzaldehyde N-(3-methylphenyl)thiosemicarbazone
-
pH 7.2, 37C
0.287
-
4-hydroxybenzaldehyde N-(4-chlorophenyl)thiosemicarbazone
-
pH 7.2, 37C
0.043
-
4-hydroxybenzaldehyde N-(4-hydroxyphenyl)thiosemicarbazone
-
pH 7.2, 37C
0.014
-
4-hydroxybenzaldehyde N-(4-methylphenyl)thiosemicarbazone
-
pH 7.2, 37C
0.045
-
4-hydroxybenzaldehyde N-(4-nitrophenyl)thiosemicarbazone
-
pH 7.2, 37C
0.242
-
4-hydroxybenzaldehyde N-phenylthiosemicarbazone
-
pH 7.2, 37C
0.5
-
4-methoxyphenol
-
-
0.0026
-
peptide Fmoc-P6
-
yeast enzyme
-
0.031
-
peptide P7
-
yeast enzyme
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0000045
-
-
partially purified enzyme, CDP reduction
0.00028
-
-
partially purified enzyme
0.0131
-
-
purified subunit L2 assayed in the presenc of L1
0.015
-
-
purified subunit L1 assayed in the presenc of L2, specific for CDP
0.0237
-
-
-
0.024
-
-
subunit Y1, expressed in Saccharomyces cerevisiae
0.035
-
-
recombinant R1 subunit, CDP reduction in the presence of ATP
0.048
-
-
recombinant DELTA1-248 R1 subunit, CDP reduction in the presence of ATP
0.062
-
-
M1 subunit from a mutant cell line of S49 T-lymphoma cells
0.122
-
-
recombinant enzyme
0.18
-
-
recombinant R2 subunit, CDP reduction in the presence of ATP
0.28
-
-
CDP reduction of subunit R1E in the presence of subunit R2F
0.3
-
-
His-tagged subunit Y2-K387N, expressed in Saccharomyces cerevisiae
0.51
-
P95484
pH 7.5, 80C
0.53
-
-
subunit R2F
0.59
-
-
purified subunit B1
0.83
-
-
CDP reduction of subunit R2F in the presence of subunit R1E
2.86
-
-
purified subunit B2
4.21
-
-
recombinant subunit B2
4.3
-
Herpes simplex virus
-
Herpes simplex virus type 2 enzyme, CDP reduction
6.3
-
-
recombinant B2 subunit
22
-
-
pH 7.5, 25C, anaerobic incubation and assay
52
-
-
iron-loaded enzyme, cosubstrate dithiothreitol, presence of 3 mM ATP, pH 7.6, 37C
66
-
-
pH 7.5, 25C, anaerobic incubation, aerobic assay
106
-
-
iron-loaded enzyme, cosubstrate thioredoxin YosR, presence of 3 mM ATP, pH 7.6, 37C
116
-
-
pH 7.5, 25C, aerobic incubation and assay
116
-
-
mutant R265Y, pH 7.5, 37C
125
-
-
iron-loaded enzyme, cosubstrate thioredoxin A, presence of 3 mM ATP, pH 7.6, 37C
146
-
-
manganese-loaded enzyme, cosubstrate dithiothreitol, presence of 3 mM ATP, pH 7.6, 37C
283
-
-
mutant R265A, pH 7.5, 37C
997
-
-
manganese-loaded enzyme, cosubstrate thioredoxin YosR, presence of 3 mM ATP, pH 7.6, 37C
1100
-
-
mutant R265E, pH 7.5, 37C
1475
-
-
manganese-loaded enzyme, cosubstrate thioredoxin A, presence of 3 mM ATP, pH 7.6, 37C
2750
-
-
wild-type, pH 7.5, 37C
10000
-
P21524
substrate ADP, mutant R293A, pH 7.6, 30C
40000
-
P21524
substrate ADP, mutant Q288A, pH 7.6, 30C
50000
-
P21524
substrate CDP, mutant R293A, pH 7.6, 30C
60000
-
P21524
substrate CDP, mutant Q288A, pH 7.6, 30C
190000
-
P21524
substrate CDP, wild-type, pH 7.6, 30C
258000
-
P21524
substrate ADP, wild-type, pH 7.6, 30C
additional information
-
-
extracts from hydroxyurea resistant cell line HU-7 exhibit a 13fold higher ADP reductase activity and a 5fold higher CDP reductase activity when compared to wild-type
additional information
-
-
optimal activity in 40 mM 4-(2-hydroxyethyl)-1-piperazineethansulfonic acid, pH 7.6, 80-120 mM KCl
additional information
-
-
strong increase of specific activity during growth of Novikoff hepatoma cells
additional information
-
-
activities of recombinant wild-type R1/R2 and chimeric wild-type R2 with truncated R1 mutant DELTA1-248
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
7
Scenedesmus obliquus
-
-
7.2
-
-
catalytic activity assay at
7.2
-
-
assay at
7.4
-
-
assay at
7.5
-
-
ligand binding assay at
7.5
-
P95484
assay at
7.6
-
-
assay at
7.6
-
-
assay at
7.6
-
-
assay at
8.4
-
-
assay at
8.5
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
9.2
-
stable intermediate formation, change in the rate-limiting step at elevated pH, profiles, overview
6.8
8.8
-
60% activity at pH 7.2
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20
-
-
assay at
22
-
-
assay at
22
-
-
assay at room temperature
25
30
Scenedesmus obliquus
-
-
25
-
-
assay at
37
-
-
assay at
37
-
-
catalytic activity and ligand binding assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
80
-
P95484
assay at
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
15
42
Scenedesmus obliquus
-
15C: approx. 27% activity, 42C: approx. 10% activity
25
37
-
reaction rate is about twice as fast at 37C as the rate at 25C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Leishmania donovani MHOM/IN/1983/AG83
-
-
-
Manually annotated by BRENDA team
-
a colon adenocarcinoma cell line
Manually annotated by BRENDA team
P23921
lung and colon cancer cell lines
Manually annotated by BRENDA team
-
small cell lung carcinoma
Manually annotated by BRENDA team
-
a promyelocytic leukemia cell line
Manually annotated by BRENDA team
-
promyelocytic leukemia cell
Manually annotated by BRENDA team
-
a colon carcinoma cell line
Manually annotated by BRENDA team
-
a myelogenous leukemia cell line
Manually annotated by BRENDA team
-
nasopharyngeal carcinoma cells, a gemcitabine-resistant cell line
Manually annotated by BRENDA team
-
baby hamster kidney cells
Manually annotated by BRENDA team
-
L1210 cells resistant to specific ribonucleotide reductase inhibitors
Manually annotated by BRENDA team
Q5VRJ6, Q6K848
RNRL1 and RNRS1 are highly expressed in young leaves; RNRL1 and RNRS1 are highly expressed in young leaves
Manually annotated by BRENDA team
-
Molt 4F cells
Manually annotated by BRENDA team
-
mutant line of S49 mouse T-lymphoma cells
Manually annotated by BRENDA team
Q5VRJ6, Q6K848
RNRL1 and RNRS1 are highly expressed in the shoot base; RNRL1 and RNRS1 are highly expressed in the shoot base
Manually annotated by BRENDA team
-
neuroepithelioma cell
Manually annotated by BRENDA team
-
a breast carcinoma cell line
Manually annotated by BRENDA team
additional information
-
RNR expression in small cell lung cancer cell lines, overview
Manually annotated by BRENDA team
additional information
-
class I RNR predominates in aerobically grown cells
Manually annotated by BRENDA team
additional information
Escherichia coli K-12 CM735
-
class I RNR predominates in aerobically grown cells
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
M1 subunit is exclusively localized in cytoplasm
Manually annotated by BRENDA team
-
enzyme from Novikoff hepatoma tumor cells is associated with a smooth membrane component of the cytoplasm
Manually annotated by BRENDA team
-
during the normal cell cycle, the two large subunits Rnr1 and Rnr3 are predominantly localized to cytoplasm. Under genotoxic stress the subunits Rnr2 and Rnr4 become redistributed to the cytoplasm in a checkpoint-dependent manner
Manually annotated by BRENDA team
-
enzyme may be specifically associated with mitochondria
Manually annotated by BRENDA team
-
during the normal cell cycle, the two small subunits Rnr2 and Rnr4 are predominantly localized to nucleus. Under genotoxic stress, Rnr2 and Rnr4 become redistributed to the cytoplasm in a checkpoint-dependent manner
Manually annotated by BRENDA team
-
mainly present in mitochondrial soluble fraction
-
Manually annotated by BRENDA team
-
incubation of respiring rat liver mitochondria with [14C]cytidine diphosphate leads to accumulation of radiolabeled deoxycytidine and thymidine nucleotides within the mitochondria
Manually annotated by BRENDA team
additional information
-
RNR is located in discrete foci in a number that increases with the overlapping of replication cycles in Escherichia coli, higher amount of RNR per focus at faster growth rates
-
Manually annotated by BRENDA team
additional information
Escherichia coli K-12 CM735
-
RNR is located in discrete foci in a number that increases with the overlapping of replication cycles in Escherichia coli, higher amount of RNR per focus at faster growth rates
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Bacillus cereus (strain ATCC 14579 / DSM 31)
Bacillus cereus (strain ATCC 14579 / DSM 31)
Bacillus cereus (strain ATCC 14579 / DSM 31)
Bacillus cereus (strain ATCC 14579 / DSM 31)
Bacillus cereus (strain ATCC 14579 / DSM 31)
Bacillus cereus (strain ATCC 14579 / DSM 31)
Bacillus halodurans (strain ATCC BAA-125 / DSM 18197 / FERM 7344 / JCM 9153 / C-125)
Bacillus subtilis (strain 168)
Chlamydia trachomatis (strain D/UW-3/Cx)
Chlamydia trachomatis (strain D/UW-3/Cx)
Chlamydia trachomatis (strain D/UW-3/Cx)
Chlamydia trachomatis (strain D/UW-3/Cx)
Chlamydia trachomatis (strain D/UW-3/Cx)
Chlamydia trachomatis (strain D/UW-3/Cx)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Geobacillus kaustophilus (strain HTA426)
Geobacillus kaustophilus (strain HTA426)
Geobacillus kaustophilus (strain HTA426)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Streptococcus sanguinis (strain SK36)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
49600
-
-
isolated subunit NrdF, plus major fraction of 80100 Dalton, gel filtration
79800
-
Q81G56
subunit NrdE, SDS-PAGE and calculated
80100
-
-
isolated subunit NrdF, plus small fraction of 49600 Dalton, gel filtration
82700
-
-
isolated subunit NrdE
125900
-
-
5 mM Ca2+, gel filtration
160000
-
O69273
gel filtration
250000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 84000 + x * 58000, 84000 Da subunit is predominantly monomeric under experimental conditions, 58000 Da subunit may be oligomeric, SDS-PAGE
?
-
2 * 90000 + x * ?, Novikoff hepatoma cells
?
Scenedesmus obliquus
-
2 * 90000 + x * 75000, most likely 1 75000 Da subunit, SDS-PAGE
?
-
x * 45000 + 1 * 75000 + 1 * 45000, holoenzyme may have an alpha4,beta,beta' structure, SDS-PAGE
?
-
x * 34000, R2F subunit, DSD-PAGE
?
Corynebacterium glutamicum R163
-
x * 34000, R2F subunit, DSD-PAGE
-
dimer
-
alpha,beta, 1 * 100000 + 1 * 100000, Molt F4 lymphoblast cells
dimer
Herpes simplex virus
-
1 * 136000 + 1 * 38000, molecular weight for subunit 1 deduced from sequence: 124017 Da, difference may be due to phosphorylation, SDS-PAGE
dimer
-
2 * 60200, dimer appears to dissociate in the absence of Ca2+ into monomers, SDS-PAGE
dimer
-
alphabeta, class Ib RNR is composed of two subunits alpha (NrdE) and beta (NrdF). Beta contains the metallo-cofactor, essential for the initiation of the reduction process
dimer
Bacillus subtilis JH624
-
alphabeta, class Ib RNR is composed of two subunits alpha (NrdE) and beta (NrdF). Beta contains the metallo-cofactor, essential for the initiation of the reduction process
-
heterodimer
Q5VRJ6, Q6K848
eukaryotic RNRs comprise alpha2beta2 heterodimers, the large and small subunits show strong interaction; eukaryotic RNRs comprise alpha2beta2 heterodimers, the large and small subunits show strong interaction
heterotetramer
-
R1R2 complex
hexamer
-
4 * 45000 + 1 * 45000 + 1 * 75000, regenerating liver
monomer or dimer
-
alpha or alpha2, class II RNRs
multimer
-
alphanbetan multi-subunit protein complex consisting of subunit types RR1 and RR2, the alpha or RR1 subunit contains the catalytic C site and two allosteric sites, while the beta or RR2 subunit houses a stable tyrosyl free radical that is transferred some 35 A to the catalytic site to initiate radical-based chemistry on the substrate
octamer
-
4 * 107000, subunit NrdA + 4 * 47000, subunit NrdB, SDS-PAGE
oligomer
-
class I enzymes show a alpha2beta2 complex structure, modeling
oligomer
-
class I enzyme show a alpha2beta2 complex structure, modeling
oligomer
-
RNRs are composed of alpha- and beta-subunits that form active (alpha)n(beta)m, with n or m being 2 or 6, complexes. Subunit alpha binds NDP substrates, i.e. CDP, UDP, ADP, and GDP, C site, as well as ATP and dNTPs, i.e. dATP, dGTP, TTP, allosteric effectors that control enzyme activity (A site) and substrate specificity, S site
tetramer
-
alpha2,beta2, 160000 Da subunit B1 and 78000 Da subunit B2, each consisting of 2 identical or similar proteins
tetramer
-
2 * 84000 + 2 * 55000, SDS-PAGE
tetramer
-
alpha2beta2, 2 * 85000 + 2 * 35000, enzyme induced in Escherichia coli after infection with bacteriophage T4, SDS-PAGE
tetramer
-
alpha, alpha',beta2, 2 * 80000 + 2 * 39000, SDS-PAGE; alpha,alpha'beta2, 2 * 82000 + 2 * 78000, each subunit composed of 2 polypeptide chains, subunit B1, 82000 Da, sedimentation equilibrium centrifugation, subunit B2, low speed sedimentation equilibrium centrifugation
tetramer
-
alpha,alpha'beta2, 2 * 82000 + 2 * 78000, each subunit composed of 2 polypeptide chains, subunit B1, 82000 Da, sedimentation equilibrium centrifugation, subunit B2, low speed sedimentation equilibrium centrifugation
tetramer
-
alpha2beta2, 2 * 84000 + 2 * 43500, SDS-PAGE
tetramer
-
-
tetramer
-
alpha2,beta2, 2 * 70000 + 2 * 36000, SDS-PAGE
tetramer
-
alpha2,betabeta, 2 * 96900 (PFR1) + 1 * 40600 (PFR2) + 1 * 39000 (PFR4), SDS-PAGE
tetramer
-
2 * 160000, subunit R1, + 2 * 78000, subunit R2, the catalytic active enzyme forms a dimer of homodimers
tetramer
-
RNR is a tetramer consisting of two non-identical homodimers. The two identical M2 subunits regulate the substrate specificity of the enzyme, while the other two identical M1 subunits are responsible for the activity by binding the ribonucleotides and allosteric effectors
tetramer
-
2 * R1 subunit + 2 * R2 subunit
tetramer
-
2 * subunit R1 + 2 * subunit R2
tetramer
-
the enzyme activity requires formation of a complex between subunits R1 and R2 in which the R2 C-terminal peptide binds to R1
tetramer
-
2 * M1-subunit + 2 * M2-subunit
tetramer
-
the enzyme consists of M1, M2, and p53R2 subunits in an alphabeta2gamma constellation
tetramer
-
1:1 complex of two homodimeric subunits, hRRM1 and hRRM2
tetramer
-
4 * 37 442.98, subunit R2, mass spectrometry, 4 * 31000, recombinant subunit R2, SDS-PAGE
tetramer
-
class Ib RNR is composed of two homodimeric subunits: alpha2 or NrdE, where nucleotide reduction occurs, and beta2 or NrdF, which contains an unidentified metallocofactor that initiates nucleotide reduction
tetramer
-
alpha2beta2, with subunits alpha1, alpha2, beta1, and beta2
tetramer
-
alpha2beta2
tetramer
-
class I RNR is a tetramer formed by two homodimers, subunit R1 encoded by the nrdA gene and subunit R2 encoded by the nrdB gene
tetramer
Escherichia coli K-12 CM735
-
class I RNR is a tetramer formed by two homodimers, subunit R1 encoded by the nrdA gene and subunit R2 encoded by the nrdB gene
-
tetramer
Escherichia coli overproducing
-
alpha2,beta2, 160000 Da subunit B1 and 78000 Da subunit B2, each consisting of 2 identical or similar proteins
-
trimer
O69273
alpha,beta2, 1 * 81200 + 2 * 37900, deduced from nucleotide sequence
monomer or dimer
-
class II enzymes show a monomeric or dimeric structure
additional information
-
88000-90000 Da M1 subunits are degraded into 40000 Da fragments in proliferately quiescent liver cells, intact subunits are only accumulated when the cells replicate DNA
additional information
-
the active form of B2 subunit contains a tyrosyl radical essential for activity
additional information
Scenedesmus obliquus
-
catalytic subunit U2 contains a tyrosyl radical essential for activity
additional information
-
enzyme in Ehrlich ascites tumor cells consits of two nonidentical subunits: an effector-binding subunit, EB, and a non-heme iron containing subunit, NHI, since their relative levels are not coordinately regulated the stoichiometry of the whole enzyme varies with the cell cycle
additional information
-
the active form of B2 subunit contains a tyrosyl radical essential for activity; tyrosyl radical is stabilized by an iron center
additional information
-
composition of the enzyme is not constant, but is altered in presence of effectors
additional information
-
proposed in vitro mechanism for the assembly of the diferric tyrosyl radical cofactor of subunit R2
additional information
-
subunits Y1 and Y2 constitute the active enzyme, large subunit Y3 has no activity, subunit Y4 may function as a chaperone
additional information
-
large subunit R1 contains binding sites for substrates and allosteric effectors, smaller subunit R2 contains non-heme iron and a tyrosyl free-radical
additional information
-
nucleotide binding to the specificity site drives formation of an active R1,2R2,2 dimer, ATP or dATP binding to the adenine-specific site results in formation of an inactive tetramer and ATP binding to the hexamerization site drives formation of an active R1,6R2,6 hexamer which is probably the major active form in mammalian cells
additional information
-
each catalytic turnover by aerobic ribonucleotide reductase requires the assembly of the two proteins, R1 (alpha2) and R2 (beta2), to produce deoxyribonucleotides for DNA synthesis
additional information
Q7LG56
ribonucleoside-diphosphate reductase subunit M2 B may substitute for small enzyme subunit hRRM2 to form a functional holoenzyme with large subunit hRRM1. The holoenzyme with subunit M2 B can only achieve 40-75% kinetic activity of that with hRRM2. Both small subunits share the same binding site on large subunit hRRM1. The effectors ATP or dATP can regulate holoenzyme activity independent of the small subunit
additional information
-
enzyme consists of two homodimeric subunits, R1 and R2. In Saccharomyces cerevisiae, there are two R2 subunits named beta and beta, the active form in the holoenzyme being a dimer betabeta. Isoform beta plays a crucial role in cluster assembly
additional information
-
under normal conditions, the cell assembles stoichiometric amounts of tyrosyl radicals per betabeta subunit dimer and modulation of tyrosyl radical concentration is not involved in regulation of enzyme activity
additional information
-
enzyme is a complex of the NrdA protein harboring the active site and the allosteric sites and the NrdB protein harboring a tyrosyl radical. Wild-type enzyme consists of four NrdA and four NrdB subunits. A truncated NrdA lacking the N-terminal ATP-cone forms an NrdA2NrdB2 complex
additional information
-
in presence of dTTP, subunit R1 forms dimers. In presence of dATP or ATP, subunit R1 forms hexamers of 544000 Da, which interact with the subunit R2 dimer to form an enzymatically active protein complex alpha6beta2. The complex can be in activated or inhibited state depending on whether ATP or dATP is bound. Complex alpha6beta2 is the major form of enzyme at physiological levels of subunits and nucleotides
additional information
-
2 * R1 subunit + 2 * R2 subunit, cross-talk Between the C-terminus of one subunit R1 monomer and the active site of its neighboring monomer, overview
additional information
-
C-terminal domain of subunit R1 acts in trans to reduce the active site of its neighbouring monomer and interacts with the N-terminal domain of neighbouring R1. Inhibitor protein Sml1 competes with the C-terminal domain of R1 for association with the N-terminal domain to hinder the accessibility of the CX2C motif to the active site for R1 regeneration during the catalytic cycle
additional information
O84835
interaction of the alpha2 and beta2 subunits during the reaction, comparison to the RNR from Escherichia coli, overview
additional information
-
interaction of the alpha2 and beta2 subunits during the reaction, comparison to the RNR from Chlamydia trachomatis, overview
additional information
-
one monomer can swivel between two conformations and impose significant influences on helix D and helix B of the opposite monomer. This change ultimately affects the orientation of D100 and, thus, the integrity of the binuclear iron environment. Structural basis of B helix disorder and the N-terminal swivel region, overview
additional information
-
hybrid holoenzyme, consisting of the small manganese-containing R2F subunit and the large catalytic subunit R1E
additional information
-
class I RNRs are composed of a heterotetramer, which is in turn composed of two homodimers of the R1 and R2 subunits. The R1 subunit contains the active site as well as the sites for allosteric regulation
additional information
-
structure comparisons of classI-III RNRs, model for the subunit organization of RNRs, overview
additional information
-
subunit R1 contains the substrate binding site and catalyzes dehydroxylation of the 2'-hydroxyl group of the ribose ring. The tyrosine radical in R2 is in the neutral deprotonated form with the oxidized Fe(III)Fe(III) active site
additional information
-
structures of the active holoenzymes of class I-III RNRs, structure comparisons, overview
additional information
-
dATP-induced oligomerization, overview, modeling of the holo-complex
additional information
-
at physiological concentrations, alpha-subunit NrdE is a monomer and beta-subunit NrdF in complex with dimanganic-tyrosyl radical cofactor is a dimer. A 1:1 mixture of NrdE:NrdF, however, is composed of a complex mixture of structures
additional information
P00452
a complex between alpha2 and beta2 subunits forms an unprecedented alpha4beta4 ring-like structure in the presence of the negative activity effector dATP, while the active conformation is alpha2beta2. Under physiological conditions, the enzyme exists as a mixture of transient alpha2beta2 and alpha4beta4 species whose distributions are modulated by allosteric effectors. This interconversion between entails dramatic subunit rearrangements
additional information
Bacillus subtilis JH624
-
at physiological concentrations, alpha-subunit NrdE is a monomer and beta-subunit NrdF in complex with dimanganic-tyrosyl radical cofactor is a dimer. A 1:1 mixture of NrdE:NrdF, however, is composed of a complex mixture of structures
-
additional information
Corynebacterium glutamicum R163
-
hybrid holoenzyme, consisting of the small manganese-containing R2F subunit and the large catalytic subunit R1E
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
subunit R2, X-ray diffraction structure determination and analysis at 2.75-2.90 A resolution
-
R2F, sitting drop vapour diffusion method, at 4C, mixing 0.001 ml of RNR solution, containing mM KCl, 50 mM TrisHCl, 2 mM DTT, 15% glycerol, pH 7.5, with 0.001 ml of reservoir buffer solution containing 0.1 M sodium citrate, 27.5% PEG 4000, 0.05 M ammonium acetate, pH 6.0, and 0.1 M ammonium acetate pH 7.0 with 0.05 MTris-HCl, pH 7.5, X-ray diffraction structure determination and analysis at 1.36 A resolution
-
B2 subunit, hanging drop method, crystallization in 20% polyethylene glycol 4000, 200 mM NaCl, 0.3% dioxane, 50 mM ethyl mercuric thiosalicylate, 50 mM MES buffer, pH 6.0, orthorhombic crystals, crystal structure at 2.2 A resolution
-
B2 subunit, hanging drops of 0.01 ml containing 25 mg/ml of enzyme with 1 ml of 1.5 M ammonium sulfate in the well and 750 mM ammonium sulfate starting concentration in the drop, pH 6.0, crystals appear after 1 week at room temperatur
-
complex between NrdIox and MnII 2-NrdF, Two NrdI and two NrdF molecules are present in the asymmetric unit, X-ray diffraction structure determination and analysis at 2.5 A resolution
P37146
free radical subunit R2, basic motif is a bundle of eight long helices. R2 dimer has two equivalent dinuclear iron centers. Iron atoms have both histidine and carboxyl acid ligands and are bridged by the carboxylate group of E115. The essential residue Y122 is buried inside the protein and the tyrosyl radical cannot participate directly in hydrogen abstraction
-
mutant Y122H of R2 protein subunit
-
structure of a complex between alpha2 and beta2 subunits forming an unprecedented alpha4beta4 ring-like structure in the presence of the negative activity effector dATP, while the active conformation is alpha2beta2. Under physiological conditions, the enzyme exists as a mixture of transient alpha2beta2 and alpha4beta4 species whose distributions are modulated by allosteric effectors. This interconversion between entails dramatic subunit rearrangements
P00452
two-dimensional crystals of B1 dimer enzyme-effector complex, 18 A resolution
-
purified recombinant His6-tagged hp53R2, sitting drop vapor diffusion method, at 25C, 0.002 ml of 4.5 mg/ml protein in 20 mM Tris, pH 7.5, are mixed with 150 mM NaCl and 0.002 ml of precipitant solution containing 0.1 M sodium citrate, pH 6.45, 1.3 M Li2SO4, and 0.5 M (NH4)2SO4, reservoir volume is 0.250 ml, 7-14 days, addition of ferrous ammonium sulfate of 5 mM 1 h prior to harvesting, X-ray diffraction structure determination and analysis at 2.6 A resolution
-
subunit RR1 in complex with TTP, dATP, TTP/GDP, TTP/ATP, and TTP/dATP, 1. TTP bound at the S-site, 2. dATP bound at the S-site, 3. TTP bound at the S-site and GDP at the C-site, 4. TTP bound at the S-site and ATP at the A-site, and 5. TTP bound at the S-site and dATP at the A-site, X-ray diffraction structure determination and analysis at resolutions of 2.4 A, 2.3 A, 3.2 A, 3.1 A, and 3.1 A, respectively
-
small subunit R2 of ribonucleotide reductase, at 4C and 20C, 10 mg/ml protein in 20 mM HEPES, pH 7.5, 300 mM NaCl, 10% glycerol, 0.1 mg/ml chymotrypsin, and 0.1 M hexamine cobalt(III) chloride, is mixed with optimized reservoir solution containing 14% w/v PEG 8000, 0.2 M MgCl2,0.1 M Tris-HCl pH 8.2, optimization of the crystallization conditions, X-ray diffraction structure determination and analysis at 2.0 A resolution
-
alpha subunit, in apo form, in complex with AMP analogue 5'-adenylyl-beta,gamma-imidodiphosphate, with 5'-adenylyl-beta,gamma-imidodiphosphate and CDP, with 5'-adenylyl-beta,gamma-imidodiphosphate and UDP, with dGTP and ADP, TTP and GDP. Binding of specificity effector rearranges loop 2 and moves residue P294 out of the catalytic site, accomodating substrate binding. substrate binding further rearranges loop2. Cross-talk occurs largely through R293 and Q288 of loop 2. Substrate ribose binds with its 3 hydroxyl closer than its 2 hydroxyl to residue C218 of the catalytic redox pair
-
purified enzyme, formed by recombinant subunits R2 and R4, complexed with inhibitor peptide P7 or peptide Fmoc-P6, 20 mg/ml protein in 0.1 M HEPES, pH 7.5, with 20 mM TTP, 5% glycerol, 5mM DTT, 0.1 M KCL, and 25 mm MgCl2, is mixed with a reservoir solution containing 20-25% PEG 3350, 0.2 M NaCl, and 100 mM HEPES, pH 7.5, soaking of crystals for 4 h in reservoir solution with added inhibitor peptide P6 or P7, followed by soaking of crystals in 25% PEG 3350, 0.2 M NaCl, and 100 mM HEPES, pH 7.5, supplemented with 15% glycerol, X-ray diffraction structure determination and analysis at 2.6 and 2.5 A resolution, respectively
-
structures of mutanr R293A complexed with dGTP and AMPPNP-CDP reveal that ADP is not bound at the catalytic site, and CDP binds farther from the catalytic site compared to wild type
P21524
subunit Rnr1 in complex with gemcitabine diphosphate or with a beta subunit Rnr2 or Rnr4 derived peptide. Binding of gemcitabine diphosphate is different from binding of its analogue CDP. Rnr2 and Rnr4 peptides bind differently from each other and block the formation of the enzyme complex
-
low-resolution crystal structure of an alpha2beta2 complex
-
hanging drop method, crystal structures of the dimeric class II RNR in complex with four cognate allosteric specificity effector-substrate pairs (dTTP-GDP, dGTP-ADP, dATP-CDP or dATP-UDP), as well as structures with only the different effectors (dATP, dTTP or dGTP)
O33839
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50
-
Herpes simplex virus
-
half-life: 2.5 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dithiothreitol, 1 mM, stabilizes
-
protein concentrations above 5 mg/ml stabilizes
-
effector-binding subunit of mammalia is more sensitive to proteolysis by chymotrypsin, to heating at 55C and to sulfhydryl reagents e.g. p-chloromercuribenzoate and N-ethylmaleimide, than the nonheme iron subunit, the latter is more sensitive to trypsin treatment
-
glycerol and ATP required for stabilization
-
partially purified enzyme is very unstable in solution, half-life at 0C: less than 24 h
-
quite susceptible to denaturation
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the enzyme is not stable to to reactive oxygen and nitrogen species, RO(N)S, produced by the hosts immune system
-
685235
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70, 50 mM Tris-HCl, pH 7.6, 100 mM KCl, several months, no loss of activity
-
-70C, 100 mM potassium phosphate, pH 7.0, 1 mM dithiothreitol, enzyme concentration 4.8 mg/ml, 6 months, no loss of activity
-
-70C, up to 8 months, no loss of activity
Herpes simplex virus
-
4C, at least 24 h, no loss of activity
Herpes simplex virus
-
-15C or -70C, 10 mM histidine-HCl, pH 7.0, 2 mM dithiotreitol, 40% glycerol, 2 mM ATP, 6 months, no loss of activity
-
-15C, 10 mM histidine-HCl, pH 7.0, 2 mM dithiotreitol, 2 mM ATP, 6 months, 80% loss of activity
-
-70C, 10 mM histidine-HCl, pH 7.0, 2 mM dithiothreitol, 2 mM ATP, 6 months 60% loss of activity
-
-80C, 0.25 M sucrose, 100 mM Tris-HCl, pH 7.6, 10 mM MgCl2, 2 mM dithiothreitol, 1 month, no loss of activity
-
quick-freezing in liquid nitrogen and subsequent storage at -20C, several weeks, no loss of activity
-
-80C, several months, no loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant R2F from Escherichia coli strain BL21(DE3) by ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
isolation of beta-subunit NrdF using anion exchange chromatography to separate apo-/mismetalated-NrdFs from dimanganic-tyrosyl radical cofactor
-
recombinant NrdI, NdE, NrdF, and YmaB from Escherichia coli. The absorption spectra of the purified NrdENrdF complex exhibited characteristics of a Mn(III)2-Y radical center with 2 Mn/beta2 and 0.5 Y radical/beta2
-
streptomycin, ammonium sulfate, DEAE-cellulose, hydroxylapatite, dATP-Sepharose
-
recombinant wild-type R1 and R2 subunits and F127Y, Y129F and F127Y/Y129F R2 mutant subunits
-
low-salt precipitation, DEAE-cellulose, Supredex 200, Mono Q
O69273
recombinant R2F by anion exchange chromatography, gel filtration, and another different step of anion exchange chromatography to homogeneity
-
native R2F subunit by 2',5'-ADP affinity and hydrophobic interaction chromatography, followed by two different steps of gel filtration, an further by anion exchange chromnatography for metallo-cofactor analysis
-
enzyme induced in Escherichia coli after infection with bacteriophage T4, streptomycin, ammonium sulfate, dATP-Sepharose
-
chimeric R2 genes in which C-terminal sequences in Escherichia coli subunit R2 are replaced by C-terminal sequences from the mouse subunit R2
-
chimeric R2 genes in which C-terminal sequences in Escherichia coli subunit R2 are replaced by C-terminal sequences from the mouse subunit R2; overproducing strain
-
chimeric R2 genes in which C-terminal sequences in Escherichia coli subunit R2 are replaced by C-terminal sequences from the mouse subunit R2; recombinant B2 subunit, Sephadex G-25, DEAE Bio gel, Sephadex QAE-50
-
native NrdF from strain GR536
-
HSV type 2
Herpes simplex virus
-
streptomycin sulfate, ammonium sulfate, partial purification
Herpes simplex virus
-
recombinant His-tagged alpha and beta subunits by affinity chromatography
-
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
recombinant His6-tagged subunits hRRM1 and hRRM2 from Escherichia coli strain BL21(DE3)
-
recombinant His6-tagged subunits M2, p53R2, and M1 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged ORF60 protein, subunit R2, from Escherichia coli BL21 (DE3) by metal affinity chromatography and gel filtration
-
chimeric R2 genes in which C-terminal sequences in Escherichia coli subunit R2 are replaced by C-terminal sequences from the mouse subunit R2
-
M1 subunit from a mutant cell line of S49 T-lymphoma cells
-
Novikoff ascites tumor cells, partial
-
Y370F and Y370w mutant enzymes
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nicke affinity chromatography and gel filtration
-
ammonium sulfate, Sephadex G-200, dATP-Sepharose
-
ammonium sulfate, Sephadex G-200, partially purified; partial
-
gel filtration, ATP-agarose, partial purification
-
regenerating liver, dATP-Sepharose affinity chromatography
-
recombinant His-tagged subunits R2 and R4 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis
-
R1E subunit, ammonium sulfate, DEAE-Sepharose, dATP-Sepharose; R2F subunit, ammonium sulfate, DEAE-Sepharose, Mono Q, Superdex
-
-
Scenedesmus obliquus
-
streptomycin, DEAE-Sepharose, Phenyl-Sepharose, Heparin-Sepharose, Sephacryl S-200
-
ammonium sulfate, Blue Sepharose, affinity resin
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression analysis of AtRNR2-like catalytic subunit gene AtRNR2A, phylogenetic analysis. Transcriptional changes of 17-days-old Arabidopsis plants, enriched in S-phase cells over younger seedlings, in response to the replication-blocking agent hydroxyurea and to the DNA double-strand break inducer bleomycin; expression analysis of AtRNR2-like catalytic subunit gene AtRNR2B, phylogenetic analysis. Transcriptional changes of 17-days-old Arabidopsis plants, enriched in S-phase cells over younger seedlings, in response to the replication-blocking agent hydroxyurea and to the DNA double-strand break inducer bleomycin; expression analysis of the AtRNR2-like catalytic subunit gene TSO2, phylogenetic analysis. Transcriptional changes of 17-days-old Arabidopsis plants, enriched in S-phase cells over younger seedlings, in response to the replication-blocking agent hydroxyurea and to the DNA double-strand break inducer bleomycin
P50651, Q6Y657, Q9LSD0
expression of R2F in Escherichia coli strain BL21(DE3)
-
expression of N-terminally tagged NrdE and NrdF, the RNR genes are organized within the nrdI-nrdE-nrdF-ymaB operon, recombinant expression of NrdI, NdE, NrdF, and YmaB in Escherichia coli. For overexpression, the entire operon is placed behind a Pspank(hy) promoter and integrated into the Bacillus subtilis genome at the amyE site. Removal of the tag from rNrdE and rNrdF, leaving three amino acids GSH, has little effect on activity
-
expression of nrdA and nrdB genes encoding a CDP reductase in Escherichia coli
-
expression of wild-type and amino terminal deleted DELTA1-248 R1 subunit and wild-type, F127Y, Y129F and F127Y/Y129F mutant R2 subunit in Escherichia coli
-
expression of wild-type R2 and R1 and of truncated R1 mutant DELTA1-248 in Escherichia coli
-
overexpression of wild-type and mutant R2 subunits in Escherichia coli strain BL21(DE3)
-
expression R1E and R2F subunits in Escherichia coli
O69273
recombinant expression of R2F using expression vector pOCA2
-
expression of chimeric R2 genes in which C-terminal sequences in Escherichia coli subunit R2 are replaced by C-terminal sequences from the mouse subunit R2
-
expression of Y122F, Y356F and Y122F/Y356F mutant enzymes in Escherichia coli
-
genes nrdA and nrdB, expression of FLAG-tagged subunits R1 and R2 in Escherichia coli strains CMT931 and CMT933
-
overexpression of B2 subunit
-
Herpes simplex virus type I and II
Herpes simplex virus
-
-
P31350
expression of His-tagged alpha and beta subunits and of His-tagged mutant alpha-subunit
-
expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3)
-
expression of His6-tagged subunits hRRM1 and hRRM2 in Escherichia coli strain BL21(DE3)
-
expression of His6-tagged subunits M2, p53R2, and M1 in Escherichia coli strain BL21(DE3)
-
recombinant overexpression of the ORF60 protein, subunit R2, with an N-terminal extension, MGPHHHHHHLESTSLYKKAGS in Escherichia coli BL21 (DE3) cells. The N-terminal extension encompasses an attB1 site for the gateway recombination event and a His tag to facilitate protein purification
-
expression analysis of mouse RRM2 protein in Hep-G2 cells
-
expression of M1 mutant cDNA containing a G to A transition at codon 57 in chinese hamster ovary cells
P11157
expression of wild-type and Y177F mutant subunit R2 in Escherichia coli
-
expression of Y370F and Y370W mutant enzymes in Escherichia coli
-
nearly full length cDNA of M1 and M2 subunits, expression of M2 subunit in mouse 3T6 cells and monkey COS-7 cells
-
gene Rv3051c, expression of the His-tagged enzyme in Escherichia coli strain Bl21(DE3)
-
genes V3 and St1, gene mapping, DNA and amino acid sequence determination and analysis; genes V3 and St1, gene mapping, DNA and amino acid sequence determination and analysis. Complementation of a yeast mutant
Q5VRJ6, Q6K848
expression of His-tagged subunits R2 and R4 in Escherichia coli strain BL21(DE3)
-
expression of subunits Y1, Y2, Y3 and Y4 in Escherichia coli, expression of Y1, His-tagged Y2 and His tagged Y2-K387N mutant enzyme subunit in Saccharomyces cerevisiae
-
expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
RNR genes are induced in cells grown in Luria-Bertani medium, with levels of NrdE and NrdF elevated 35fold relative to that of the wild-type strain
-
RNR genes are induced in cells grown in Luria-Bertani medium, with levels of NrdE and NrdF elevated 35fold relative to that of the wild-type strain
Bacillus subtilis JH624
-
-
class Ib RNR is expressed under iron-limited and oxidative stress conditions
-
isoform NrdEF is induced during H2O2 stress. Induction is mediated by the inactivation of Fur, an iron-dependent repressor. NrdEF supports cell replication in iron-depleted cells. Iron binds to NrdF when it is expressed in iron-rich cells, but NrdEF is functional only in cells that are both iron-depleted and manganese-rich
P39452
ribonucleotide reductase subunit mRNA levels are comparably low in both damaged and undamaged G1 cells and highly induced in damaged S/G2 cells. Transcript numbers becomes correlated with both protein levels and localization only upon DNA damage in a cell cycle-dependent manner. The differential ribonucleotide reductase response to DNA damage correlates with variable Mec1 kinase activity in the cell cycle in single cells. The transcription of ribonucleotide reductase genes is noisy and non-Poissonian in nature
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
morme
P50651, Q6Y657, Q9LSD0
AtRNR2B induction is abolished in the rad9-rad17 double mutant, transgenic plant phenotypes, overview
F127Y
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similar CDP reductase activity as wild-type
W51F
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site-directed mutagenesis, the decay of the Mn(IV)/Fe(IV) intermediate is slightly affected
Y129F
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no CDP reductase activity
Y222F
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the substitution by site-directed mutagenesis retards the intrinsic decay of the Mn(IV)/Fe(IV) intermediate by about 10fold and diminishes the ability of ascorbate to accelerate the decay by about 65fold but has no detectable effect on the catalytic activity of the Mn(IV)/Fe(III)-R2 product
Y338F
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site-directed mutagenesis, substitution of Y338, the cognate of the subunit interfacial R2 residue in the R1 S R2 PCET pathway of the conventional class I RNRs, has almost no effect on decay of the Mn(IV)/Fe(IV) intermediate but abolishes catalytic activity
G392S
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temperature-sensitive protein with complete splicing activity at 17 and 28C but not at 37C or higher
C225A
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4-6% of wild-type activity
C225S
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C225 appears to be one of the participants in the direct reduction of substrate
C225S
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major product formed by interaction with CDP is cytosine
C439A
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4-6% of wild-type activity
C439S
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the C439S mutant of the Escherichia coli R1 is catalytically inactive in vitro
C462S
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in the presence of dithiothreitol the major product formed by interaction with CDP is cytosine
C754A
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active with dithiothreitol as reductant, 3% of wild type activity with thioredoxin
C759A
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active with dithiothreitol as reductant, 3% of wild type activity with thioredoxin
C759S
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C759 may play a role in the relay of electrons between thioredoxin and subunit B1
N238A
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the monomeric R1 protein is able to dimerize when bound by both substrate and effector and is able to reduce ribonucleotides with a comparatively high capacity
W48A/Y122F
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the reaction remains at the level of the peroxo-intermediate, structural analysis
W48F/D84E
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the reaction remains at the level of the peroxo-intermediate, structural analysis
Y122F
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mutant enzyme cannot generate a Y122 tyrosyl radical necessary for catalysis, 0.5% of wild-type activity
Y122F
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subunit R2, study on kinetics of decay of W48 cation radical
Y122F/Y356F
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0.5% of wild-type activity
Y122F/Y356F
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subunit R2, study on kinetics of decay of W48 cation radical
Y122H
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the specific activity of mutant enzyme preparation is less than 0.5% of the wild-type activity. Mutant of R2 protein subunit, the mutant contains a novel stable paramagnetic center, named H. Deteiled characterization of center H, using 1H2H-14N/15N- and 57Fe-EDDOR in comparison with the FeIIIFeIV intermediate X observed in the iron reconstitution reaction of R2, a new tyrosyl radical on Phe208 as ligand to the diiron center
Y356F
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similar properties as wild-type
Y356F
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subunit R2, study on kinetics of decay of W48 cation radical
Y730F
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site-directed mutagenesis, the mutant excludes a direct superexchange mechanism between C439 and Y731 in radical transport, overview
D16R
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site-directed mutagenesis, the mutant retains 55% of wild-type activity for CDP reduction, and 67% for ADP reduction, it is not inhibited and does not form hexamers at physiologically relevant dATP concentrations
D57N
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site-directed mutagenesis, the mutant is not inhibited and does not form hexamers at physiologically relevant dATP concentrations, the mutation of Asp 57 to Asn abolishes the salt-bridge and change the electrostatic environment of the A-site, resulting in loss of allosteric regulation by dATP
D57N
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site-directed mutagenesis, binding kinetics to clofarabine di- and triphosphate inhibitors compared to the wild-type enzyme, overview
H2E
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site-directed mutagenesis, the mutant retains 56% of wild-type activity for CDP reduction, and 56% for ADP reduction
K95E
P31350
mutation in small subunit M2, results in dimer disassembly and enzyme activity inhibition. Mutant is capable of generating the diiron and tyrosyl radical cofactor, but the disassembly of the M2 dimer reduces its interaction with the large subunit M1. The transfection of the wild-type M2 but not the K95E mutant rescues theG1/S phase cell cycle arrest and cell growth inhibition caused by the siRNA knockdown of M2
D57N
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mutation in R1 subunit, in contrast to wild-type dATP stimulates CDP reduction, GDP reduction is inhibited by dGTP, ADP reduction is inhibited by dTTP similar to wild-type, this suggests that the mutant enzyme binds both ATP and dATP to the activity site but does not distinguish between them when it comes to catalysis
R265A
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mutant in subunit R2, about 10% of wild-type activity. Mutant is able to form stable tyrosyl radicals and bind subunit R1 with similar kinetics as wild-type
R265E
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mutant in subunit R2, about 40% of wild-type activity. Mutant is able to form stable tyrosyl radicals and bind subunit R1 with similar kinetics as wild-type
R265Q
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mutant in subunit R2, about 1% of wild-type activity. Mutant is able to form stable tyrosyl radicals and bind subunit R1 with similar kinetics as wild-type
R265Y
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mutant in subunit R2, about 4% of wild-type activity. Mutant is able to form stable tyrosyl radicals and bind subunit R1 with similar kinetics as wild-type
Y177F
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tyrosyl residue involved in radical formation
Y370F
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mutation in R2 subunit, no activity
C428S
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mutantion is lethal. Cells carrying both the C428S and the SX2S mutation of CX2C motif on plasmids are viable and form colonies with an efficiency similar to that of the wild-type control showing interallelic complementation
Q288A
P21524
mutation causes severe S phase defects in cells that use the enzyme as the sole source of of ribonucleoside diphosphate activity. Compared to the wild-type enzyme activity, Q288A mutants show 15% of ADP reduction, whereas they show 23% of CDP reduction. There is a 6fold loss of affinity for ADP binding and a 2fold loss of affinity for CDP. Q288A can support mitotic growth, albeit with a severe S phase defect
R293A
P21524
mutation causes lethality in cells that use the enzyme as the sole source of ribonucleoside diphosphate activity. Compared to the wild-type enzyme activity, R293A mutants show 4% of ADP reduction, whereas they show 20% CDP reduction. The mutant is unable to bind ADP and binds CDP with 2fold lower affinity compared to wild-type. X-ray structures of R293A complexed with dGTP and AMPPNP reveal that ADP is not bound at the catalytic site, and CDP binds farther from the catalytic site compared to wild type. R293A cannot support mitotic growth
additional information
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insertion of homing endonuclease gene mobE into the nrdA gene coding for the large subunit of ribonucleotide-diphosphate reductase. The insertion splits nrdA into two independent genes but does not inactivate NrdA function. The reconstituted complex of NrdA-a, NrdA-b and sunbunit NrdB has enzymic activity
additional information
P50651, Q6Y657, Q9LSD0
atTSO2 transcription is only activated in response to double-strand breaks dependent upon AtE2Fa. ATso2 mutant is hypersensitive to bleomycin, transgenic plant phenotypes, overview; early AtRNR2A induction is decreased in an atr mutant, rnr2a mutants are hypersensitive to hydroxyurea, transgenic plant phenotypes, overview
F127Y/Y129F
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10-15% of wild-type CDP reductase activity
additional information
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construction of truncated R1 mutant DELTA1-248
G392S/C539G
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the cleavage at the ribonucleotide reductase RIR1 intein C-terminus is blocked, but other cleavage activities can be efficiently performed at 17C. The mutant variant possesses the properties of low-temperature-induced cleavage at the intein N-terminus
additional information
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mutations of resiude C539, the N-terminal residue of the C-extein in the ribonucleotide reductase RIR1 protein, lead to changes of pattern and level of protein-splicing activities
D84E
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the mutation provides a ligand environment similar to that found in methane monooxygenase, MMO, renders this residue bidentate, and Glu204 becomes monodentate. The RNR mutant, however, remains distinct from MMO, which has a beta-1,1 type Glu-bridge, most likely due to the effects of second sphere residues
additional information
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site-specific replacement of Y356 with 3,4-dihydroxyphenylalanine in the beta2 subunit and trapping the 3,4-dihydroxyphenylalanine radical intermediate in the presence of alpha2 subunit dimer, substrate and effector ATP or TTP. 3,4-Dihydroxyphenylalanine radical formation shows fast and slow phases, rapid phases are substrate-mediated conformational changes that place about 50% of the alpha2beta2 complex into an active conformation for turnover. Substrate plays a major role in conformational gating
K95E/E98K
P31350
charge-exchanging double mutation, recovers the dimerization and activity lost in mutant K95E
additional information
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expression of subunit R2 siRNA 1284, targeting the AA(N19) sequence motif, inhibits R2 expression and active enzyme complex formation in different cell lines, it also inhibits cell growth and proloferation in vitro by blocking in the S-phase of the cell cycle, overview
D57N
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mutant of the catalytic subunit mR1 is not inhibited by dATP because of a block in the formation of R1(4b)
additional information
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transfection of RRM2 protein-expressing Hep-G2 cells with constructed potent siRNA, NM_009104, inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo, overview
Y370W
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mutation in R2 subunit, point mutation does not affect the ability to form a normal diferric iron/tyrosyl radical center, 1.7% of wild-type activity probably due to slow radical transfer
additional information
Q5VRJ6, Q6K848
construction of transgenic plants using Agrobacterium tumefaciens-mediated transformation. Complementation by gene construct introduction into calli generated from the mature embryos of v3 and st1 mutant kernels, respectively. The stripe1 mutant in Oryza sativa produces chlorotic leaves in a growth stage-dependent manner under field conditions. It is a temperature-conditional mutants that produces bleached leaves at a constant 20C or 30C, but almost green leaves under diurnal 30C/20C conditions, phenotype, overview. Expression profiles of genes associated with chloroplast development in mutant plants; construction of transgenic plants using Agrobacterium tumefaciens-mediated transformation. Complementation by gene construct introduction into calli generated from the mature embryos of v3 mutant kernels, respectively. The virescent3 mutant in Oryza sativa produces chlorotic leaves in a growth stage-dependent manner under field conditions. It is a temperature-conditional mutant that produces bleached leaves at a constant 20C or 30C, but almost green leaves under diurnal 30C/20C conditions, phenotype, overview. Expression profiles of genes associated with chloroplast development in mutant plants
additional information
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truncated NrdA lacking the N-terminal ATP-cone forms an NrdA2NrdB2 complex. Mutant protein is completely resistant to high concentrations of dATP
K387N
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affords higher activity due to increased tyrosyl radical content
additional information
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deletion of C-terminal domain of subunit R1 is lethal. Mutation of CX2C motif to SX2S results in viable, but slowly growing cells. Mutant cells exhibit a prolonged S phase
additional information
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construction of heterochimeric enzymes as heterocomplexes containing mammalian R2 C-terminal heptapeptide P7, Ac-1FTLDADF7, and its peptidomimetic P6, 1Fmoc(Me)PhgLDChaDF7, bound to Saccharomyces cerevisiae R1, ScR1, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pharmacology
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inhibition of RNRs is a proven strategy for combating cancer and some viruses
drug development
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the enzyme is an important therapeutic target for anticancer drugs
medicine
P23921
in transgenic human lung and colon cancer lines expressing xanthine oxidase regulatory subunit RRM1, G2 cell cycle arrest, apoptosis, and efficient DNA damage repair are induced
medicine
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combination of (2E)-2-(anthracen-9-ylmethylidene)-N-hydroxyhydrazinecarboximidamide with the first-line antileukemic agent arabinofuranosylcytosine, Ara-C, synergistically potentiates the antineoplastic effects of Ara-C
medicine
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thiosemicarbazone chelators 2-[di(pyridin-2-yl)methylidene]-N,N-dimethylhydrazinecarbothioamide and 2-(diphenylmethylidene)-N,N-dimethylhydrazinecarbothioamide possess potent and selective antitumor activity and may have an additional mechanism of ribonucleotide reductase inhibition via their effects on major thiol-containing systems
medicine
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in transgenic mice expressing xanthine oxidase regulatory subunit RRM1, carcinogen-induced lung tumor formation is significantly suppressed. RRM1 transgenic animals repair chemically induced DNA damage with greater efficiency than control animals
medicine
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ribonucleotide reductase is a therapeutic target for DNA replication-dependent diseases such as cancer in humans
medicine
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the enzyme is a target for cancer therapy
medicine
Q7LG56
skin fibroblasts isolated from a patient with a lethal homozygous missense mutation of ioform p53R2 grow normally in culture with an unchanged complement of mtDNA. During active growth, the four dNTP pools do not differ in size from normal controls, whereas during quiescence, the dCTP and dGTP pools decrease to 50% of the control. On withdrawal of ethidium bromide depleting cell of mitochondrial DNA, mitochondrial DNA recovers equally well in cycling mutant and control cells, whereas during quiescence, the mutant fibroblasts remain deficient. Addition of deoxynucleosides to the medium increases intracellular dNTP pools and normalizes mtDNA synthesis. Quiescent mutant fibroblasts are also deficient in the repair of UV-induced DNA damage
additional information
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the enzyme is a target for drug design against the parasite
additional information
Leishmania donovani MHOM/IN/1983/AG83
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the enzyme is a target for drug design against the parasite
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