1.17.4.1: ribonucleoside-diphosphate reductase
This is an abbreviated version!
For detailed information about ribonucleoside-diphosphate reductase, go to the full flat file.
Word Map on EC 1.17.4.1
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1.17.4.1
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deoxyribonucleotides
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hydroxyurea
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tyrosyl
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reductases
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chlamydia
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trachomatis
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deoxynucleotides
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proton-coupled
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diiron
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deoxycytidine
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diferric
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thiyl
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dntps
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dcdp
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thiosemicarbazone
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diferric-tyrosyl
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nrdabs
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hydroxyurea-resistant
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medicine
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nrdef
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heterodinuclear
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drug development
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antiferromagnetically
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pharmacology
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molecular biology
- 1.17.4.1
- deoxyribonucleotides
- hydroxyurea
-
tyrosyl
- reductases
- chlamydia
- trachomatis
-
deoxynucleotides
-
proton-coupled
-
diiron
- deoxycytidine
-
diferric
-
thiyl
- dntps
- dcdp
- thiosemicarbazone
-
diferric-tyrosyl
-
nrdabs
-
hydroxyurea-resistant
- medicine
-
nrdef
-
heterodinuclear
- drug development
-
antiferromagnetically
- pharmacology
- molecular biology
Reaction
Synonyms
2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase, ADP reductase, CDP reductase, class I ribonucleotide reductase, class I ribonulceotide reductase, class I RNR, class I RR, class Ia ribonucleotide reductase, class Ia RNR, class Ia RR, class Ib ribonucleotide reductase, class Ib RNR, class Ic ribonucleotide reductase, class II RNR, manganese-ribonucleotide reductase, Mn-RNR, More, mRR, NrdA, NrdB, NrdE, NrdF, nucleoside diphosphate reductase, p53-inducible ribonucleotide reductase, R2F, reductase, ribonucleoside diphosphate, ribonucleoside 5'-diphosphate reductase, ribonucleoside diphosphate reductase, ribonucleoside-diphosphate reductase subunit M2 B, ribonucleotide diphosphate reductase, ribonucleotide reductase, RIR1, RIR2, RNR, RNR1 rRibonucleoside-diphosphate reductase large chain 1, RNR2, UDP reductase
ECTree
1.17.4.1 ribonucleoside-diphosphate reductaseAdvanced search results
results (
results (Activating Compound
Activating Compound on EC 1.17.4.1 - ribonucleoside-diphosphate reductase
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ACTIVATING COMPOUND 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
2-mercaptoethanol
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25 mM, maximal activation, 70% of activity with dithiothreitol
dithioerythritol
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0.5 mM, maximal activation, 94% of activity with dithiothreitol
EDTA
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reversible stimulation of GDP reduction, irreversible inhibition of CDP reduction
P1,P4-bis(5'-adenosyl) tetraphosphate
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stimulation at low concentrations, inhibition above 0.3 mM
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
adenyl-5'-yl-imidodiphosphate
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can replace ATP as activator of CDP and UDP reduction
adenyl-5'-yl-imidodiphosphate
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stimulation at low concentration, inhibition above 0.3 mM
ATP
binding of deoxynucleoside triphosphate effectors (ATP/dATP, dGTP, and dTTP) modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. The unprotonated N1 of adenosine is the primary determinant of ATP/dATP-directed specificity for CDP
ATP
binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop. The unprotonated N1 of adenosine is the primary determinant of ATP/dATP-directed specificity for CDP. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
ATP
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activity of the enzyme is tightly regulated via two allosteric sites, the specificity site (s-site) and the overall activity site (a-site). The a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and functions as an on/off switch, whereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce. The class I ribonucleotide reductase has a duplicated ATP cone domain. Each alpha polypeptide binds three dATP molecules, and the N-terminal ATP cone is critical for binding two of the dATPs because a truncated protein lacking this cone could only bind dATP to its s-site. ATP activates the enzyme solely by preventing dATP from binding. The dATP-induced inactive form is an alpha4 complex, which can interact with beta2 to form a non-productive alpha4beta2 complex. Other allosteric effectors induce a mixture of alpha2 and alpha4 forms, with the former being able to interact with beta2 to form active alpha2beta2 complexes
ATP
overall activity is stimulated by ATP and downregulated by dATP via a genetically mobile ATP cone domain mediating the formation of oligomeric complexes with varying quaternary structures
ATP
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binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop. The unprotonated N1 of adenosine is the primary determinant of ATP/dATP-directed specificity for CDP. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
ATP
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activation by ATP has a regulatory function
dATP
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dATP maximally stimulates CDP reduction at 8-10 microM followed by rapid inhibition at higher concentrations
dATP
the binding of effector dATP alters the active site to select for pyrimidines over purines. 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
dATP
binding of deoxynucleoside triphosphate effectors (ATP/dATP, dGTP, and dTTP) modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. The unprotonated N1 of adenosine is the primary determinant of ATP/dATP-directed specificity for CDP
dATP
binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop.. The unprotonated N1 of adenosine is the primary determinant of ATP/dATP-directed specificity for CDP. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
dATP
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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
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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
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activity of the enzyme is tightly regulated via two allosteric sites, the specificity site (s-site) and the overall activity site (a-site). The a-site resides in an N-terminal ATP cone domain that binds dATP or ATP and functions as an on/off switch, whereas the composite s-site binds ATP, dATP, dTTP, or dGTP and determines which substrate to reduce. The class I ribonucleotide reductase has a duplicated ATP cone domain. Each alpha polypeptide binds three dATP molecules, and the N-terminal ATP cone is critical for binding two of the dATPs because a truncated protein lacking this cone could only bind dATP to its s-site. ATP activates the enzyme solely by preventing dATP from binding. The dATP-induced inactive form is an alpha4 complex, which can interact with beta2 to form a non-productive alpha4beta2 complex. Other allosteric effectors induce a mixture of alpha2 and alpha4 forms, with the former being able to interact with beta2 to form active alpha2beta2 complexes
dATP
overall activity is stimulated by ATP and downregulated by dATP via a genetically mobile ATP cone domain mediating the formation of oligomeric complexes with varying quaternary structures
dATP
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0.005 mM, stimulation of CDP reduction in absence of ATP, inhibition in presence of ATP
dATP
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binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop.. The unprotonated N1 of adenosine is the primary determinant of ATP/dATP-directed specificity for CDP. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
dATP
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strong stimulation of CDP reduction
dGTP
the binding of effector dGTP 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
dGTP
binding of deoxynucleoside triphosphate effectors (ATP/dATP, dGTP, and dTTP) modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. The O6 and protonated N1 of dGTP direct specificity for ADP
dGTP
binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop. The O6 and protonated N1 of dGTP direct specificity for ADP. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
dGTP
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binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop. The O6 and protonated N1 of dGTP direct specificity for ADP. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
dGTP
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slight stimulation of CDP reduction
dithiothreitol
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optimal in vitro activity with 10 mM, inhibition above
dTTP
binding of deoxynucleoside triphosphate effectors (ATP/dATP, dGTP, and dTTP) modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. The 5-methyl, O4, and N3 groups of dTTP contributes to specificity for GDP
dTTP
binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
dTTP
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only binds to the specificity site (s-site), is able to stimulate tetramer formation
dTTP
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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
dTTP
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binding of deoxynucleoside triphosphate effectors ATP/dATP, dGTP, and dTTP modulates the specificity of class I ribonucleotide reductase for CDP, UDP, ADP, and GDP substrates. dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop. Interactions with the effector nucleobase alter loop 2 geometry, resulting in changes in specificity among the four NDP substrates of ribonucleotide reductase
dTTP
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slight stimulation of CDP reduction
E. coli thioredoxin reductase
Tequatrovirus T4
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enzyme induced in Escherichia coli by infection with bacteriophage T4
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NrdI
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
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NrdI
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is an essential player in Escherichia coli class Ib RNR cluster assembly, overview. Preparation of recombinant N-terminally His6-tagged NrdI
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phosphate
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up to 50 mM, pH 6.7: necessary for activity, decrease of activity at higher values
additional information
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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
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additional information
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ribonucleoside effectors are exclusively bound at effector binding sites on subunit B1 controlling substrate specificity and activity
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additional information
enzyme activation mechanism and kinetics, overview
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additional information
mechanism for the activation of peroxy intermediates in binuclear non-heme iron enzymes for reactivity
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additional information
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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
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additional information
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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
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additional information
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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
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additional information
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overview: nucleoside 5'-diphosphates as effectors of mammalian ribonucleotide reductase
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additional information
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comprehensive and quantitative model for allosteric control of mRR enzymatic activity based on molecular mass, ligand binding and enzyme activity studies
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