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Information on EC 1.17.4.1 - ribonucleoside-diphosphate reductase and Organism(s) Pseudomonas aeruginosa

for references in articles please use BRENDA:EC1.17.4.1

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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 (α-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).

The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
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 RNR
nucleoside diphosphate reductase
-
-
-
-
reductase, ribonucleoside diphosphate
-
-
-
-
ribonucleoside 5'-diphosphate reductase
-
-
-
-
ribonucleoside diphosphate reductase
-
-
-
-
ribonucleotide diphosphate reductase
-
-
-
-
ribonucleotide reductase
-
-
-
-
UDP reductase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
MetaCyc
adenosine deoxyribonucleotides de novo biosynthesis I, 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)
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
LITERATURE
COMMENTARY hide
Reversibility
r=reversible
ir=irreversible
?=not specified
CDP + reduced dithiothreitol
2'-dCDP + oxidized dithiothreitol + H2O
show the reaction diagram
-
Substrates: -
Products: -
?
CDP + thioredoxin
2'-dCDP + thioredoxin disulfide + H2O
show the reaction diagram
-
Substrates: -
Products: -
?
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
Substrates: class I and class II RNRs
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY hide
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
nucleoside 5'-diphosphate + thioredoxin
2'-deoxynucleoside 5'-diphosphate + thioredoxin disulfide + H2O
show the reaction diagram
-
Substrates: class I and class II RNRs
Products: -
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
-
iron is bound tightly to the protein. Enzyme activity is the same in presence and absence of EDTA
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
not inhibitory: EDTA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dTTP
-
only binds to the specificity site (s-site), is able to stimulate tetramer formation
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
116
-
pH 7.5, 25┬░C, aerobic incubation and assay
22
-
pH 7.5, 25┬░C, anaerobic incubation and assay
66
-
pH 7.5, 25┬░C, anaerobic incubation, aerobic assay
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
top print hide Go to Organism Search
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Highest Expressing Human Cell Lines
Cell Line Links Gene Links
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
the enzyme catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides, which are used as building blocks for DNA replication and repair
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
A0A2R3IPR0_PSEAI
963
0
107133
TrEMBL
-
A0A8G5NQS1_PSEAI
963
0
107147
TrEMBL
-
A0A8G7KP33_PSEAI
963
0
107110
TrEMBL
-
A0A241XS89_PSEAI
953
0
104499
TrEMBL
-
A0A8G2XSS4_PSEAI
734
0
82670
TrEMBL
-
A0A367MF63_PSEAI
734
0
82723
TrEMBL
-
A0A8F9VBI6_PSEAI
963
0
107134
TrEMBL
-
A0A4P0TE96_PSEAI
349
1
39622
TrEMBL
-
A0A8G2RL33_PSEAI
734
0
82682
TrEMBL
-
A0A8G5FP03_PSEAI
963
0
107120
TrEMBL
-
A0A8G1K486_PSEAI
963
0
107105
TrEMBL
-
A0A8H1AJ21_PSEAI
963
0
107106
TrEMBL
-
A0A8G3MLK0_PSEAI
734
0
82737
TrEMBL
-
A0A3S0LZ02_PSEAI
963
0
107163
TrEMBL
-
A0A8G3T940_PSEAI
734
0
82693
TrEMBL
-
A0A3M5DRQ5_PSEAI
979
0
108957
TrEMBL
-
A0A444M5W0_PSEAI
963
0
107134
TrEMBL
-
A0A8G3U7G3_PSEAI
734
0
82751
TrEMBL
-
A0A8G3Q4V6_PSEAI
415
1
47377
TrEMBL
-
A0A8G6JVA7_PSEAI
963
0
107078
TrEMBL
-
A0A8G2U013_PSEAI
734
0
82749
TrEMBL
-
A0A6H3G4S4_PSEAI
734
0
82649
TrEMBL
-
A0A072ZKL0_PSEAI
963
0
107106
TrEMBL
-
A0A8G2QYX7_PSEAI
734
0
82694
TrEMBL
-
A0A8F9K0K5_PSEAI
963
0
107080
TrEMBL
-
A0A8G6ICT1_PSEAI
963
0
107120
TrEMBL
-
B3G0Y7_PSEAI
415
1
47387
TrEMBL
-
A0A8G6NX99_PSEAI
963
0
107164
TrEMBL
-
A0A367LXQ0_PSEAI
123
0
13961
TrEMBL
-
A0A8G3B199_PSEAI
963
0
107078
TrEMBL
-
A0A8G6FU24_PSEAI
734
0
82651
TrEMBL
-
A0A5E5R3D5_PSEAI
734
0
82723
TrEMBL
-
A0A8G4M937_PSEAI
963
0
107078
TrEMBL
-
A0A0A8RNJ6_PSEAI
415
1
47358
TrEMBL
-
A0A4P0TC40_PSEAI
66
0
7797
TrEMBL
-
A0A8G4HLK6_PSEAI
734
0
82737
TrEMBL
-
A0A8G4N7D3_PSEAI
734
0
82783
TrEMBL
-
A0A3S0J0Q4_PSEAI
734
0
82735
TrEMBL
-
A0A8G2RRJ2_PSEAI
734
0
82705
TrEMBL
-
A0A485ELQ0_PSEAI
419
1
47758
TrEMBL
-
A0A367M3Q7_PSEAI
592
0
66459
TrEMBL
-
A0A8F8R8C2_PSEAI
734
0
82699
TrEMBL
-
A0A8G7CN14_PSEAI
734
0
82651
TrEMBL
-
A0A8G7KXL7_PSEAI
963
0
107122
TrEMBL
-
A0A8B5BN77_PSEAI
415
1
47385
TrEMBL
-
A0A3M5DSY1_PSEAI
435
1
49514
TrEMBL
-
A0A8G2VT99_PSEAI
963
0
107152
TrEMBL
-
A0A8G4NU06_PSEAI
734
0
82725
TrEMBL
-
A0A8G6LDQ9_PSEAI
734
0
82693
TrEMBL
-
A0A071L157_PSEAI
734
0
82709
TrEMBL
-
A0A8G3QBU6_PSEAI
734
0
82669
TrEMBL
-
A0A8G6FXX2_PSEAI
963
0
107106
TrEMBL
-
A0A211UQM9_PSEAI
734
0
82732
TrEMBL
-
A0A8G6KDI3_PSEAI
963
0
107087
TrEMBL
-
A0A8G2YLQ3_PSEAI
734
0
82624
TrEMBL
-
A0A8F9JSD8_PSEAI
734
0
82678
TrEMBL
-
A0A5K1SD81_PSEAI
962
0
106978
TrEMBL
-
A0A8G3YNW2_PSEAI
963
0
107136
TrEMBL
-
A0A7M2ZUH8_PSEAI
963
0
107136
TrEMBL
-
A0A8G2ZBU6_PSEAI
963
0
107136
TrEMBL
-
A0A8G7M7N9_PSEAI
963
0
107092
TrEMBL
-
A0A8G7CXT5_PSEAI
963
0
107134
TrEMBL
-
A0A0A8RN63_PSEAI
930
0
103719
TrEMBL
-
A0A5K1SIW7_PSEAI
734
0
82651
TrEMBL
-
A0A8G3PAQ8_PSEAI
963
0
107078
TrEMBL
-
A0A8G3AC49_PSEAI
734
0
82695
TrEMBL
-
A0A8G2WTF0_PSEAI
963
0
107105
TrEMBL
-
A0A8G3LYN6_PSEAI
734
0
82709
TrEMBL
-
A0A8G7KFQ6_PSEAI
963
0
107078
TrEMBL
-
A0A5E5QXT0_PSEAI
963
0
107166
TrEMBL
-
A0A8G4CX59_PSEAI
415
1
47417
TrEMBL
-
A0A8F9PHN0_PSEAI
416
1
47444
TrEMBL
-
A0A2R3ISJ9_PSEAI
714
0
80420
TrEMBL
-
A0A8G3D2A6_PSEAI
734
0
82737
TrEMBL
-
A0A6B9LCH6_PSEAI
269
0
28790
TrEMBL
-
A0A367MIR2_PSEAI
129
0
14052
TrEMBL
-
A0A485EMU5_PSEAI
640
0
71370
TrEMBL
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
107000
-
4 * 107000, subunit NrdA + 4 * 47000, subunit NrdB, SDS-PAGE
428000
tetramer, calculated from sequence
47000
-
4 * 107000, subunit NrdA + 4 * 47000, subunit NrdB, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
beta-subunit is predominantly a dimer, whereas the alpha-subunit is in a nucleotide-dependent equilibrium between monomers, dimers, and tetramers. The alpha2beta2 complex is the major active form
homotetramer
4 * 107106, calculated from sequence
monomer
-
beta-subunit is predominantly a dimer, whereas the alpha-subunit is in a nucleotide-dependent equilibrium between monomers, dimers, and tetramers. The alpha2beta2 complex is the major active form
monomer or dimer
-
class II enzymes show a monomeric or dimeric structure
octamer
-
4 * 107000, subunit NrdA + 4 * 47000, subunit NrdB, SDS-PAGE
oligomer
-
class I enzyme show a alpha2beta2 complex structure, modeling
tetramer
-
beta-subunit is predominantly a dimer, whereas the alpha-subunit is in a nucleotide-dependent equilibrium between monomers, dimers, and tetramers. The alpha2beta2 complex is the major active form
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop method
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E106A/E126A
mutant enzyme completely loses the ability to be inhibited by dATP. Like the wild-type protein the mutant enzyme can bind approximately three dATP per polypeptide. The mutant enzyme loses the ability to tetramerize and only forms dimers regardless of allosteric effector
H72A/D73A/Y830A
the mutant enzyme forms inactive tetramers in the presence of any allosteric effector, the mutant enzyme partially loses its propensity to be inhibited by dATP. Like the wild-type protein the mutant enzyme can bind approximately three dATP per polypeptide
R119D
mutant enzyme completely loses the ability to be inhibited by dATP. Like the wild-type protein the mutant enzyme can bind approximately three dATP per polypeptide. The mutant enzyme loses the ability to tetramerize and only forms dimers regardless of allosteric effector
additional information
-
truncated NrdA lacking the N-terminal ATP-cone forms an NrdA2NrdB2 complex. Mutant protein is completely resistant to high concentrations of dATP
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 (DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Torrents, E.; Westman, M.; Sahlin, M.; Sjoeberg, B.M.
Ribonucleotide reductase modularity: Atypical duplication of the ATP-cone domain in Pseudomonas aeruginosa
J. Biol. Chem.
281
25287-25296
2006
Pseudomonas aeruginosa
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
Jonna, V.R.; Crona, M.; Rofougaran, R.; Lundin, D.; Johansson, S.; Braennstroem, K.; Sjoeberg, B.M.; Hofer, A.
Diversity in overall activity regulation of ribonucleotide reductase
J. Biol. Chem.
290
17339-17348
2015
Pseudomonas aeruginosa
Manually annotated by BRENDA team
Johansson, R.; Jonna, V.R.; Kumar, R.; Nayeri, N.; Lundin, D.; Sjoeberg, B.M.; Hofer, A.; Logan, D.T.
Structural mechanism of allosteric activity regulation in a ribonucleotide reductase with double ATP cones
Structure
24
906-917
2016
Pseudomonas aeruginosa (Q9I4I1), Pseudomonas aeruginosa
Manually annotated by BRENDA team