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Information on EC 1.17.4.1 - ribonucleoside-diphosphate reductase and Organism(s) Escherichia coli and UniProt Accession P00452

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IUBMB Comments
This enzyme is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. There are three types of this enzyme differing in their cofactors. Class Ia enzymes contain a diiron(III)-tyrosyl radical, class Ib enzymes contain a dimanganese-tyrosyl radical, and class II enzymes contain adenosylcobalamin. In all cases the cofactors are involved in generation of a transient thiyl (sulfanyl) radical on a cysteine residue, which attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl (alpha-oxoalkyl) radical. The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. The disulfide bridge is reduced by the action of thioredoxin. cf. EC 1.1.98.6, ribonucleoside-triphosphate reductase (formate) and EC 1.17.4.2, ribonucleoside-triphosphate reductase (thioredoxin).
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Escherichia coli
UNIPROT: P00452
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Word Map
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
Synonyms
ribonucleoside diphosphate reductase, cdp reductase, class i rnr, class i ribonucleotide reductase, class ia rnr, ribonucleoside-diphosphate reductase, class ia ribonucleotide reductase, adp reductase, p53-inducible ribonucleotide reductase, class ic ribonucleotide reductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase
-
-
-
-
ADP reductase
-
-
-
-
CDP reductase
-
-
-
-
class I ribonucleotide reductase
-
class I ribonulceotide reductase
-
class I RNR
class Ia ribonucleotide reductase
-
-
class Ia RNR
class Ib ribonucleotide reductase
class Ib RNR
class II RNR
-
cf. EC 1.17.4.2
nucleoside diphosphate reductase
-
-
-
-
reductase, ribonucleoside diphosphate
-
-
-
-
ribonucleoside 5'-diphosphate reductase
-
-
-
-
ribonucleoside diphosphate reductase
-
-
-
-
ribonucleotide diphosphate reductase
-
-
-
-
ribonucleotide reductase
UDP reductase
-
-
-
-
additional information
-
class I ribonucleotide reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2'-deoxyribonucleoside 5'-diphosphate + thioredoxin disulfide + H2O = ribonucleoside 5'-diphosphate + thioredoxin
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
2'-deoxyribonucleoside-5'-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. There are three types of this enzyme differing in their cofactors. Class Ia enzymes contain a diiron(III)-tyrosyl radical, class Ib enzymes contain a dimanganese-tyrosyl radical, and class II enzymes contain adenosylcobalamin. In all cases the cofactors are involved in generation of a transient thiyl (sulfanyl) radical on a cysteine residue, which attacks the substrate, forming a ribonucleotide 3'-radical, followed by water loss to form a ketyl (alpha-oxoalkyl) radical. The ketyl radical is reduced to 3'-keto-deoxynucleotide concomitant with formation of a disulfide anion radical between two cysteine residues. A proton-coupled electron-transfer from the disulfide radical to the substrate generates a 3'-deoxynucleotide radical, and the final product is formed when the hydrogen atom that was initially removed from the 3'-position of the nucleotide by the thiyl radical is returned to the same position. The disulfide bridge is reduced by the action of thioredoxin. cf. EC 1.1.98.6, ribonucleoside-triphosphate reductase (formate) and EC 1.17.4.2, ribonucleoside-triphosphate reductase (thioredoxin).
CAS REGISTRY NUMBER
COMMENTARY hide
9047-64-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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 + thioredoxin
2'-dADP + thioredoxin disulfide + H2O
show the reaction diagram
benzimidazoleriboside diphosphate + reduced thioredoxin
2'-deoxybenzimidazolriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
CDP + reduced thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
CDP + thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
CTP + reduced thioredoxin
2'-dCTP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
-
class I 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
-
-
?
purineriboside diphosphate + reduced thioredoxin
2'-deoxypurineriboside diphosphate + H2O
show the reaction diagram
-
-
-
?
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
ribonucleoside diphosphate + reduced glutaredoxin
2'-deoxyribonucleoside diphosphate + oxidized glutaredoxin + H2O
show the reaction diagram
-
-
-
ir
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
tubercidin diphosphate + reduced thioredoxin
2'-deoxytubercidin diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
14% of GDP reduction rate
-
?
UDP + reduced thioredoxin
2'-deoxy-UDP + oxidized thioredoxin + H2O
show the reaction diagram
-
-
-
-
?
UDP + thioredoxin
2'-dUDP + thioredoxin disulfide + H2O
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ADP + thioredoxin
2'-dADP + thioredoxin disulfide + H2O
show the reaction diagram
the enzyme converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair
-
-
?
CDP + thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
the enzyme converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair
-
-
?
CDP + thioredoxin
2'-deoxyCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
nucleoside 5'-diphosphate + glutaredoxin
2'-deoxynucleoside 5'-diphosphate + glutaredoxin disulfide + H2O
show the reaction diagram
-
class I 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
-
-
?
ribonucleoside 5'-diphosphate + thioredoxin
2'-deoxyribonuleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
-
-
-
?
ribonucleoside diphosphate + reduced thioredoxin
2'-deoxyribonucleoside diphosphate + oxidized thioredoxin + H2O
show the reaction diagram
-
enzyme catalyzes the first unique step in DNA synthesis
-
?
UDP + thioredoxin
2'-dUDP + thioredoxin disulfide + H2O
show the reaction diagram
the enzyme converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5'-deoxyadenosylcobalamin
-
class II enzymes
Cobalamin
-
class II enzymes
diferric(III)-tyrosyl radical cofactor
-
dimanganese(III)-tyrosyl radical cofactor
-
Fe2 III/III-Y radical cofactor
assembly, maintenance, and role in catalysis of the Fe2 III/III-Y radical cofactor of Ecbeta2 subunit, structure modelling, detailed overview
-
FMN
binding structure analysis with NrdF and NrdI, NrdF contributes to the electrostatic environment of the FMN binding pocket, overview
glutaredoxin
-
class Ia and Ib RNRs
NrdH-redoxin
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class Ib RNRs
-
thioredoxin
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
class II enzymes contain cobalamin as cofactor
Fe
-
class I enzymes contain diferric(III)-tyrosyl radical cofactor
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
Mn2+
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.
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(E)-2'-fluoromethylene-2'-deoxycytidine-5-diphosphate
-
i.e. N3dNDP, inhibitor forming a furanone intermediate. Modeling of enzyme-inhibitor complex
1,10-phenanthroline
-
-
1-methyl-1-hydroxyurea
-
10 mM, 55% inhibition
2'-azido-2'-deoxynucleotides
-
-
2'-chloro-2'-deoxycytidine 5'-diphosphate
-
-
2'-deoxy-2'-azidocytidine diphosphate
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inactivation
2'-halo-2'-deoxynucleotides
-
-
2-azido-UDP
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rapid time dependent inactivation
2-Nitro-imidazole
-
trivial name azomycin
3,4,5-Trihydroxybenzohydroxamic acid
-
-
3,4-dihydroxybenzohydroxamic acid
-
2.5 mM, 50% inhibition
3-methyl-1-hydroxyurea
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10 mM, 57% inhibition
4-Methyl-5-amino isoquinoline-1-carboxaldehyde thiosemicarbazone
-
-
8-hydroxyquinoline
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-
8-hydroxyquinoline 5-sulfonate
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-
Acetohydroxamic acid
-
-
aurintricarboxylate
-
oligomeric form
caracemide
-
-
CDP
-
competitive inhibition of UDP reduction
chlorambucil
-
-
cisplatin
Co2+
-
RNR activity chelates with copper leading to inactivation
dTTP
-
inhibition of ADP reduction
formohydroxamic acid
-
10 mM, 43% inhibition
gemcitabine
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i.e. F2dNDP, inhibitor forming a furanone intermediate. Modeling of enzyme-inhibitor complex
hydroxylamine
-
10 mM, complete inhibition
Hydroxyurea
n-Hexanohydroxamic acid
-
-
N-hydroxyguanidine
-
10 mM, 89% inhibition
N-hydroxyurethane
-
10 mM, 66% inhibition
N-Methylhydroxylamine
nucleotide analogs
-
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
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Polyhydroxybenzohydroxamic acid
-
-
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Pyridine-2-carboxaldehyde thiosemicarbazone
-
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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
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Synthetic peptides
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which specifically inhibit the activity of virus-induced enzyme
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dCTP
-
stimulation of UDP reduction
H2O2
-
activation
NrdI
-
TTP
the binding of effector TTP alters the active site to select for ADP and GDP. Crystal structures of Escherichia coli class Ia ribonucleotide reductase with all four substrate/specificity effector-pairs bound (CDP/dATP, UDP/dATP, ADP/dGTP, GDP/TTP) that reveal the conformational rearrangements responsible for this remarkable allostery. These structures delineate how ribonucleotide reductase reads the base of each effector and communicates substrate preference to the active site by forming differential hydrogen bonds, thereby maintaining the proper balance of deoxynucleotides in the cell
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.07
ATP
-
positive effector of CDP reduction
0.0015
dTTP
-
positive effector of CDP reduction
0.00013
glutaredoxin
-
-
0.22
UDP
-
-
additional information
additional information
-
pre-steady state kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.33 - 12.9
CDP
additional information
additional information
-
turnover number of wild-type and mutant proteins of R1 protein
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.007
GDP
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competitive vs. CDP
0.5
UDP
-
competitive vs. CDP
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.59
-
purified subunit B1
2.86
-
purified subunit B2
4.21
-
recombinant subunit B2
6.3
-
recombinant B2 subunit
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
-
assay at
8.4
-
assay at
8.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 9.2
-
stable intermediate formation, change in the rate-limiting step at elevated pH, profiles, overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isoform NrdA
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
class I RNR predominates in aerobically grown cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
the reduction of ribonucleoside diphosphate to deoxyribonucleoside diphosphate is the rate-limiting step in dNTP production
physiological function
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
39000
-
alpha, alpha,beta2, 2 * 80000 + 2 * 39000, SDS-PAGE
78000
-
alpha,alphabeta2, 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
80000
-
alpha, alpha,beta2, 2 * 80000 + 2 * 39000, SDS-PAGE
82000
-
alpha,alphabeta2, 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
90000
-
2 * 90000 + x * ?, Novikoff hepatoma cells
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
2 * 90000 + x * ?, Novikoff hepatoma cells
monomer or dimer
oligomer
-
class I enzymes show a alpha2beta2 complex structure, modeling
tetramer
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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
crystals are grown using the hanging drop vapor diffusion technique
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
two-dimensional crystals of B1 dimer enzyme-effector complex, 18 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C225A
-
4-6% of wild-type activity
C225S
C439A
-
4-6% of wild-type activity
C439S
-
the C439S mutant of the Escherichia coli R1 is catalytically inactive in vitro
C462S
-
in the presence of dithiothreitol the major product formed by interaction with CDP is cytosine
C754A
-
active with dithiothreitol as reductant, 3% of wild type activity with thioredoxin
C759A
-
active with dithiothreitol as reductant, 3% of wild type activity with thioredoxin
C759S
-
C759 may play a role in the relay of electrons between thioredoxin and subunit B1
D84E
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
N238A
-
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
the reaction remains at the level of the peroxo-intermediate, structural analysis
W48F/D84E
the reaction remains at the level of the peroxo-intermediate, structural analysis
Y122F
Y122F/Y356F
Y122H
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
Y730F
-
site-directed mutagenesis, the mutant excludes a direct superexchange mechanism between C439 and Y731 in radical transport, overview
additional information
-
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
chimeric R2 genes in which C-terminal sequences in Escherichia coli subunit R2 are replaced by C-terminal sequences from the mouse subunit R2
-
native NrdF from strain GR536
-
overproducing strain
-
recombinant B2 subunit, Sephadex G-25, DEAE Bio gel, Sephadex QAE-50
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
ribonucleotide reductase overexpression leads to a shortened chromosome replication (C period) compared with that of a wild-type strain
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
molecular biology
titration of ribonucleotide reductase expression can serve as a standard model system for studying the coordination between chromosome replication, cell division, and cell size
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kjoller Larsen, I.; Sjöberg, B.M.; Thelander, L.
Characterization of the active site of ribonucleotide reductase of Escherichia coli, bacteriophage T4 and mammalian cells by inhibition studies with hydroxyurea analogues
Eur. J. Biochem.
125
75-81
1982
Tequatrovirus T4, Bos taurus, Escherichia coli, Mus musculus
Manually annotated by BRENDA team
Thelander, L.; Sjöberg, B.M.; Eriksson, S.
Ribonucleoside diphosphate reductase (Escherichia coli)
Methods Enzymol.
51
227-237
1978
Escherichia coli, Escherichia coli overproducing
Manually annotated by BRENDA team
Lammers, M.; Follmann, H.
The ribonucleotide reductases - a unique group of metalloenzymes essential for cell proliferation
Struct. Bonding
54
27-91
1983
Tequatrovirus T4, Tequintavirus T5, Enterobacteria phage T6, Bos taurus, Saccharomyces cerevisiae, Oryctolagus cuniculus, Escherichia coli, Homo sapiens, Mesocricetus auratus, Mus musculus, Rattus norvegicus, Tetradesmus obliquus
-
Manually annotated by BRENDA team
Joelson, T.; Uhlin, U.; Eklund, H.; Sjöberg, B.M.; Hahne, S.; Karlsson, M.
Crystallization and preliminary crystallographic data of ribonucleotide reductase protein B2 from Escherichia coli
J. Biol. Chem.
259
9076-9077
1984
Escherichia coli
Manually annotated by BRENDA team
Salowe, S.P.; Stubbe, J.
Cloning, overproduction, and purification of the B2 subunit of ribonucleoside-diphosphate reductase
J. Bacteriol.
165
363-366
1986
Escherichia coli
Manually annotated by BRENDA team
Sahlin, M.; Sjöberg, B.M.; Backes, G.; Loehr, T.; Sanders-Loehr, J.
Activation of the iron-containing B2 protein of ribonucleotide reductase by hydrogen peroxide
Biochem. Biophys. Res. Commun.
167
813-818
1990
Escherichia coli
Manually annotated by BRENDA team
Smith, S.L.; Douglas, K.T.
Stereoselective, strong inhibition of ribonucleotide reductase from E. coli by cisplatin
Biochem. Biophys. Res. Commun.
162
715-723
1989
Escherichia coli
Manually annotated by BRENDA team
Stubbe, J.
Ribonucleotide reductases
Adv. Enzymol. Relat. Areas Mol. Biol.
63
349-419
1990
Escherichia coli, Herpes simplex virus, Mus musculus
Manually annotated by BRENDA team
Holmgren, A.
Regulation of ribonucleotide reductase
Curr. Top. Cell. Regul.
19
47-76
1981
Escherichia phage T2, Tequatrovirus T4, Tequintavirus T5, Enterobacteria phage T6, Bos taurus, Oryctolagus cuniculus, Escherichia coli, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Stubbe, J.
Ribonucleotide reductases: amazing and confusing
J. Biol. Chem.
265
5329-5332
1990
Escherichia coli
Manually annotated by BRENDA team
Larsson, A.; Reichard, P.
Enzymatic synthesis of deoxyribonucleotides. IX. Allosteric effects in the reduction of pyrimidine ribonucleotides by the ribonucleoside diphosphate reductase system of Escherichia coli
J. Biol. Chem.
241
2533-2539
1966
Escherichia coli
Manually annotated by BRENDA team
Thelander, L.
Physicochemical characterization of ribonucleoside diphosphate reductase from Escherichia coli
J. Biol. Chem.
248
4591-4601
1973
Escherichia coli
Manually annotated by BRENDA team
Nordlund, P.; Sjöberg, B.M.; Eklund, H.
Three-dimensional structure of the free radical protein of ribonucleotide reductase
Nature
345
593-598
1990
Escherichia coli
Manually annotated by BRENDA team
Nordlund, P.; Uhlin, U.; Westergren, C.; Joelsen, T.; Sjöberg, B.M.; Eklund, H.
New crystal forms of the small subunit of ribonucleotide reductase from Escherichia coli
FEBS Lett.
258
251-254
1989
Escherichia coli
Manually annotated by BRENDA team
Ribi, H.O.; Reichard, P.; Kornberg, R.D.
Two-dimensional crystals of enzyme-effector complexes: ribonucleotide reductase at 18-A resolution
Biochemistry
26
7974-7979
1987
Escherichia coli
Manually annotated by BRENDA team
Bunker, G.; Petersson, L.; Sjöberg, B.M.; Sahlin, M.; Chance, M.; Chance, B.; Ehrenberg, A.
Extended X-ray absorption fine structure studies on the iron-containing subunit of ribonucleotide reductase from Escherichia coli
Biochemistry
26
4708-4716
1987
Escherichia coli
Manually annotated by BRENDA team
Reichard, P.; Ehrenberg, A.
Ribonucleotide reductase - a radical enzyme
Science
221
514-519
1983
Escherichia coli
Manually annotated by BRENDA team
Stubbe, J.; Ator, M.; Krenitsky, T.
Mechanism of ribonucleoside diphosphate reductase from Escherichia coli. Evidence for 3-C-H bond cleavage
J. Biol. Chem.
258
1625-1630
1983
Escherichia coli
Manually annotated by BRENDA team
Atkin, C.L.; Thelander, L.; Reichard, P.; Lang, G.
Iron and free radical in ribonucleotide reductase. Exchange of iron and Mossbauer spectroscopy of the protein B2 subunit of the Escherichia coli enzyme
J. Biol. Chem.
248
7464-7472
1973
Escherichia coli
Manually annotated by BRENDA team
Sjöberg, B.M.; Gräslund, A.; Loehr, J.S.; Loehr, T.M.
Ribonucleotide reductase: a structural study of the dimeric iron site
Biochem. Biophys. Res. Commun.
94
793-799
1980
Escherichia coli
Manually annotated by BRENDA team
Petersson, L.; Gräslund, A.; Ehrenberg, A.; Sjöberg, B.M.; Reichard, P.
The iron center in ribonucleotide reductase from Escherichia coli
J. Biol. Chem.
255
6706-6712
1980
Escherichia coli
Manually annotated by BRENDA team
Engström, Y.; Eriksson, S.; Thelander, L.; Akerman, M.
Ribonucleotide reductase from calf thymus. Purification and properties
Biochemistry
18
2941-2948
1979
Bos taurus, Escherichia coli
Manually annotated by BRENDA team
Jordan, A.; Pontis, E.; Atta, M.; Krook, M.; Gibert, I.; Barbe, J.; Reichard, P.
A second class I ribonucleotide reductase in Enterobacteriaceae: characterization of the Salmonella typhimurium enzyme
Proc. Natl. Acad. Sci. USA
91
12892-12896
1994
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium
Manually annotated by BRENDA team
Tong, W.; Burdi, D.; Riggs-Gelasco, P.; Chen, S.; Edmondson, D.; Huynh, V.; Stubbe, J.; Han, S.; Arvai, A.; Tainer, J.
Characterization of Y122F R2 of Escherichia coli ribonucleotide reductase by time-resolved physical biochemical methods and X-ray crystallography
Biochemistry
37
5840-5848
1998
Escherichia coli (P69924)
Manually annotated by BRENDA team
Hamann, C.S.; Lentainge, S.; Li, L.S.; Salem, J.S.; Yang, F.D.; Cooperman, B.S.
Chimeric small subunit inhibitors of mammalian ribonucleotide reductase: a dual function for the R2 C-terminus?
Protein Eng.
11
219-224
1998
Escherichia coli, Mus musculus
Manually annotated by BRENDA team
Kolberg, M.; Logan, D.T.; Bleifuss, G.; Potsch, S.; Sjoberg, B.M.; Graslund, A.; Lubitz, W.; Lassmann, G.; Lendzian, F.
A new tyrosyl radical on Phe208 as ligand to the diiron center in Escherichia coli ribonucleotide reductase, mutant R2-Y122H. Combined X-ray diffraction and EPR/ENDOR studies
J. Biol. Chem.
280
11233-11246
2005
Escherichia coli (P69924), Escherichia coli
Manually annotated by BRENDA team
Birgander, P.L.; Bug, S.; Kasrayan, A.; Dahlroth, S.L.; Westman, M.; Gordon, E.; Sjoberg, B.M.
Nucleotide-dependent formation of catalytically competent dimers from engineered monomeric ribonucleotide reductase protein R1
J. Biol. Chem.
280
14997-15003
2005
Escherichia coli
Manually annotated by BRENDA team
Lang, P.; Gerez, C.; Tritsch, D.; Fontecave, M.; Biellmann, J.F.; Burger, A.
Synthesis of 8-vinyladenosine 5'-di- and 5'-triphosphate: evaluation of the diphosphate compound on ribonucleotide reductase
Tetrahedron
59
7315-7322
2003
Escherichia coli
-
Manually annotated by BRENDA team
Saleh, L.; Bollinger, J.M.
Cation mediation of radical transfer between Trp48 and Tyr356 during O2 activation by protein R2 of Escherichia coli ribonucleotide reductase: relevance to R1-R2 radical transfer in nucleotide reduction?
Biochemistry
45
8823-8830
2006
Escherichia coli
Manually annotated by BRENDA team
Cerqueira, N.M.; Fernandes, P.A.; Eriksson, L.A.; Ramos, M.J.
Dehydration of ribonucleotides catalyzed by ribonucleotide reductase: the role of the enzyme
Biophys. J.
90
2109-2119
2006
Escherichia coli
Manually annotated by BRENDA team
Pierce, B.S.; Hendrich, M.P.
Local and global effects of metal binding within the small subunit of ribonucleotide reductase
J. Am. Chem. Soc.
127
3613-3623
2005
Escherichia coli
Manually annotated by BRENDA team
Seyedsayamdost, M.R.; Stubbe, J.
Site-specific replacement of Y356 with 3,4-dihydroxyphenylalanine in the beta2 subunit of E. coli ribonucleotide reductase
J. Am. Chem. Soc.
128
2522-2523
2006
Escherichia coli
Manually annotated by BRENDA team
Nordlund, P.; Eklund, H.
Structure and function of the Escherichia coli ribonucleotide reductase protein R2
J. Mol. Biol.
232
123-164
1993
Escherichia coli
Manually annotated by BRENDA team
Zhang, Z.; Yang, K.; Chen, C.C.; Feser, J.; Huang, M.
Role of the C terminus of the ribonucleotide reductase large subunit in enzyme regeneration and its inhibition by Sml1
Proc. Natl. Acad. Sci. USA
104
2217-2222
2007
Saccharomyces cerevisiae, Escherichia coli
Manually annotated by BRENDA team
Cerqueira, N.M.; Fernandes, P.A.; Ramos, M.J.
Ribonucleotide reductase: a critical enzyme for cancer chemotherapy and antiviral agents
Recent Pat. Anticancer Drug Discov.
2
11-29
2007
Escherichia coli
Manually annotated by BRENDA team
Reece, S.Y.; Seyedsayamdost, M.R.; Stubbe, J.; Nocera, D.G.
Photoactive peptides for light-initiated tyrosyl radical generation and transport into ribonucleotide reductase
J. Am. Chem. Soc.
129
8500-8509
2007
Escherichia coli
Manually annotated by BRENDA team
Jiang, W.; Yun, D.; Saleh, L.; Bollinger, J.M.; Krebs, C.
Formation and function of the manganese(IV)/iron(III) cofactor in Chlamydia trachomatis ribonucleotide reductase
Biochemistry
47
13736-13744
2008
Chlamydia trachomatis (O84835), Chlamydia trachomatis, Escherichia coli (P69924)
Manually annotated by BRENDA team
Jensen, K.P.; Bell, C.B.; Clay, M.D.; Solomon, E.I.
Peroxo-type intermediates in class I ribonucleotide reductase and related binuclear non-heme iron enzymes
J. Am. Chem. Soc.
131
12155-12171
2009
Escherichia coli (P69924)
Manually annotated by BRENDA team
Offenbacher, A.R.; Vassiliev, I.R.; Seyedsayamdost, M.R.; Stubbe, J.; Barry, B.A.
Redox-linked structural changes in ribonucleotide reductase
J. Am. Chem. Soc.
131
7496-7497
2009
Escherichia coli
Manually annotated by BRENDA team
Cotruvo, J.A.; Stubbe, J.
An active dimanganese(III)-tyrosyl radical cofactor in Escherichia coli class Ib ribonucleotide reductase
Biochemistry
49
1297-1309
2010
Escherichia coli
Manually annotated by BRENDA team
Seyedsayamdost, M.R.; Yee, C.S.; Stubbe, J.
Use of 2,3,5-F(3)Y-beta2 and 3-NH(2)Y-alpha2 to study proton-coupled electron transfer in Escherichia coli ribonucleotide reductase
Biochemistry
50
1403-1411
2011
Escherichia coli
Manually annotated by BRENDA team
Cotruvo, J.A.; Stubbe, J.
Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo
Biochemistry
50
1672-1681
2011
Escherichia coli, Escherichia coli GR536
Manually annotated by BRENDA team
Sanchez-Romero, M.A.; Molina, F.; Jimenez-Sanchez, A.
Correlation between ribonucleoside-diphosphate reductase and three replication proteins in Escherichia coli
BMC Mol. Biol.
11
11
2010
Escherichia coli
Manually annotated by BRENDA team
Holmgren, A.; Sengupta, R.
The use of thiols by ribonucleotide reductase
Free Radic. Biol. Med.
49
1617-1628
2010
Saccharomyces cerevisiae, Escherichia coli, Homo sapiens, Lactobacillus leichmannii, Mus musculus
Manually annotated by BRENDA team
Han, W.G.; Noodleman, L.
DFT calculations for intermediate and active states of the diiron center with a tryptophan or tyrosine radical in Escherichia coli ribonucleotide reductase
Inorg. Chem.
50
2302-2320
2011
Escherichia coli
Manually annotated by BRENDA team
Sanchez-Romero, M.A.; Molina, F.; Jimenez-Sanchez, A.
Organization of ribonucleoside-diphosphate reductase during multifork chromosome replication in Escherichia coli
Microbiology
157
2220-2225
2011
Escherichia coli, Escherichia coli K-12 CM735
Manually annotated by BRENDA team
Logan, D.
Closing the circle on ribonucleotide reductases
Nat. Struct. Mol. Biol.
18
251-253
2011
Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica subsp. enterica serovar Typhimurium
Manually annotated by BRENDA team
Boal, A.; Cotruvo Jr., J.; Stubbe, J.; Rosenzweig, A.
Structural basis for activation of class Ib ribonucleotide reductase
Science
329
1526-1530
2010
Escherichia coli (P37146)
Manually annotated by BRENDA team
Martin, J.E.; Imlay, J.A.
The alternative aerobic ribonucleotide reductase of Escherichia coli, NrdEF, is a manganese-dependent enzyme that enables cell replication during periods of iron starvation
Mol. Microbiol.
80
319-334
2011
Escherichia coli (P39452)
Manually annotated by BRENDA team
Ando, N.; Brignole, E.J.; Zimanyi, C.M.; Funk, M.A.; Yokoyama, K.; Asturias, F.J.; Stubbe, J.; Drennan, C.L.
Structural interconversions modulate activity of Escherichia coli ribonucleotide reductase
Proc. Natl. Acad. Sci. USA
108
21046-21051
2011
Escherichia coli (P00452)
Manually annotated by BRENDA team
Zimanyi, C.M.; Chen, P.Y.; Kang, G.; Funk, M.A.; Drennan, C.L.
Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli
eLife
5
e07141
2016
Escherichia coli (P00452 and P69924), Escherichia coli
Manually annotated by BRENDA team
Olshansky, L.; Pizano, A.A.; Wei, Y.; Stubbe, J.; Nocera, D.G.
Kinetics of hydrogen atom abstraction from substrate by an active site thiyl radical in ribonucleotide reductase
J. Am. Chem. Soc.
136
16210-16216
2014
Escherichia coli
Manually annotated by BRENDA team
Zhu, M.; Dai, X.; Guo, W.; Ge, Z.; Yang, M.; Wang, H.; Wang, Y.P.
Manipulating the bacterial cell cycle and cell size by titrating the expression of ribonucleotide reductase
mBio
8
e01741-17
2017
Escherichia coli (P00452 and P69924)
Manually annotated by BRENDA team