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Escherichia coli K-12 substr. MG1655 Enzyme: ribonucleoside diphosphate reductase 1

Synonyms: ribonucleotide reductase I, RDPR-I

Subunit composition of ribonucleoside diphosphate reductase 1 = [(NrdA)2][(NrdB)2]
         ribonucleoside diphosphate reductase 1, α subunit dimer = (NrdA)2
                 ribonucleoside diphosphate reductase 1, α subunit = NrdA
         ribonucleoside diphosphate reductase 1, β subunit dimer = (NrdB)2
                 ribonucleoside diphosphate reductase 1, β subunit, ferritin-like = NrdB

Summary:
Ribonucleoside-diphosphate reductase (RDPR) catalyzes the conversion of nucleotides to deoxynucleotides, an essential step in DNA synthesis. All four ribonucleoside diphosphates are reduced by RDPR. Glutaredoxin may substitute for thioredoxin in the reaction. The enzyme consists of two non-identical subunits, proteins R1 and R2 (also called α and β or B1 and B2). Separately the subunits are catalytically inactive, but in the presence of Mg2+ they combine to form the enzymatically active complex. The substrate specificity is regulated by allosteric effectors (dATP, ATP, dTTP, dGTP) which bind to the R1 protein. The R1 protein also contains the redox-active thiols in each of its two active sites and five cysteine residues required for activity. The R2 subunit contains a unique cofactor, a binuclear iron center and organic free radical which arises from the oxidation of a single tyrosine residue of the subunit. The tyrosyl radical is essential for activity. A multienzyme complex is needed to activate the tyrosyl radical. The activating system is composed of three proteins, FMN reductase, superoxide dismutase and protein fraction named fraction b whose function is poorly defined. The enzyme has been crystallized. [Brown69, Thelander73, Salowe87, Nordlund90, Stubbe90, Casado91, Mao92, Allard92, Uhlin94, Coves95]

Due to the importance of this enzyme it has been the subject of many more recent laboratory investigations, including its role in chromosome replication [Odsbu09, SanchezRomero10, Salguero11, SanchezRomero11, Salguero11a] and repair [Gon11]; regulation of the amount and activity of this enzyme in the cell [Olliver10]; biochemical studies of the protein coupled electron transfer pathway [Yokoyama10a] and radical intermediate formation [Minnihan11]; and biophysical studies of subunit conformational changes [Hassan08, Offenbacher09, Rofougaran08] and the reaction mechanism [Crona10, Zipse09, Shanmugam09, Seyedsayamdost09, Artin09, Minnihan09, Crona10, Yokoyama10]. Alternative electron transfer via dihydrolipoamide for the reduction of ribonucleotide reductase has also been demonstrated in an evolved strain of E. coli [Feeney11].

Numerous crystal structures of wild-type, mutant, or derivatized NrdA and NrdB have been determined. These structures, along with accompanying physicochemical and biochemical studies, have aided in elucidating details of the reaction mechanism [Nordlund90, Uhlin94, Berardi99, Andersson99, Voegtli00, Assarsson01, Hogbom03, Voegtli03, Kolberg05, Sommerhalter05, Yokoyama10a, Yokoyama10, Minnihan11].

Ribonucleotide reductase catalyzes the rate-limiting step in DNA biosynthesis. Its central role in DNA replication and repair makes its regulation important to ensure appropriate pools of deoxyribonucleotides for these processes. Three major classes I, II and III have been designated that share similar catalytic mechanisms. Enterobacteria, including Escherichia coli and Salmonella enterica serovar Typhimurium contain class Ia (encoded by nrdA and nrdB), class Ib (encoded by nrdE and nrdF) and class III (encoded by nrdD) enzymes. Class Ia and Ib enzymes are active under aerobic conditions, while class III enzymes are inactivated by oxygen and function under strictly anaerobic conditions. Although there are differences in structure and cofactor use, their catalytic mechanisms involve a transient cysteinyl radical at the active site that inititates ribonucleotide reduction. Regeneration of the enzymes is accomplished by corresponding reductive enzyme systems [Gon06] and discussed in [Torrents07].

This enzyme is a class 1a ribonucleotide reductase. In these aerobic enzymes the radical is generated and transferred to the active site from a diferric tyrosyl radical cofactor. Studies suggest that modulation of the active diferric tyrosyl radical cofactor through biosynthetic and maintenance pathways (via the product of gene yfaE and a ferredoxin reductase), and a regulatory pathway, may be an in vivo regulatory mechanism [Hristova08, Wu07]. Although the mechanism of tyrosyl radical formation and long-range electron transfer is not yet understood, the structure of intermediates in diferric cluster assembly have been investigated using spectroscopic and electronic methods [Mitic07].

Reviews: [Brignole12, Reichard10, Kolberg04, Stubbe90a, Stubbe90]

Gene-Reaction Schematic: ?

Credits:
Last-Curated ? 03-Jan-2012 by Fulcher C , SRI International


Enzymatic reaction of: ribonucleoside-diphosphate reductase (ribonucleoside diphosphate reductase 1)

Synonyms: ribonucleotide reductase, RDPR, 2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin 2'-oxidoreductase

EC Number: 1.17.4.1

an oxidized thioredoxin + a 2'-deoxyribonucleoside 5'-diphosphate + H2O <=> a reduced thioredoxin + a ribonucleoside diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

Summary:
The reduction of CDP, UDP, GDP and ADP by purified enzyme from Escherichia coli strain KK546 has been shown using a coupled spectrophotometric assay in which the oxidation of NADPH was measured [Thelander78].

Cofactors or Prosthetic Groups: Fe2+ , Mg2+ [Comment 1]

Activators (Unknown Mechanism): ATP [Thelander78]

Inhibitors (Competitive): dCDP [Allard92]

Inhibitors (Irreversible): peroxynitrite [Guittet00]

Inhibitors (Unknown Mechanism): cisplatin [Helmward89, Smith89] , 2'-azido-2'-deoxyuridine-5'-diphosphate [Stubbe90a, Salowe87] , 2'-chloro-2'-deoxyuridine-5'-diphosphate [Stubbe90a] , dATP [Brown69]

Primary Physiological Regulators of Enzyme Activity: ATP , dATP


Enzymatic reaction of: CDP reductase (ribonucleoside diphosphate reductase 1)

EC Number: 1.17.4.1

dCDP + an oxidized thioredoxin + H2O <=> CDP + a reduced thioredoxin

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. coli) , superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis , pyrimidine deoxyribonucleotides de novo biosynthesis I

Summary:
Glutaredoxin may substitute for thioredoxin in the reaction.

The reduction of CDP by purified enzyme from Escherichia coli strain KK546 has been shown using a coupled spectrophotometric assay in which the oxidation of NADPH was measured [Thelander78].


Enzymatic reaction of: UDP reductase (ribonucleoside diphosphate reductase 1)

EC Number: 1.17.4.1

dUDP + an oxidized thioredoxin + H2O <=> UDP + a reduced thioredoxin

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis (E. coli) , superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis , pyrimidine deoxyribonucleotides de novo biosynthesis I

Summary:
Glutaredoxin may substitute for thioredoxin in the reaction.

The reduction of UDP by purified enzyme from Escherichia coli strain KK546 has been shown using a coupled spectrophotometric assay in which the oxidation of NADPH was measured [Thelander78]. The reduction of [3H]UDP was demonstrated in ether-permeabilized cells of Escherichia coli CR34, a derivative of E. coli K-12 [Filpula77].


Enzymatic reaction of: ADP reductase (ribonucleoside diphosphate reductase 1)

EC Number: 1.17.4.1

dADP + an oxidized thioredoxin + H2O <=> ADP + a reduced thioredoxin

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible.

In Pathways: superpathway of histidine, purine, and pyrimidine biosynthesis , superpathway of purine nucleotides de novo biosynthesis II , superpathway of adenosine nucleotides de novo biosynthesis II , adenosine deoxyribonucleotides de novo biosynthesis II

Summary:
Glutaredoxin may substitute for thioredoxin in the reaction.

The reduction of ADP by purified enzyme from Escherichia coli strain KK546 has been shown using a coupled spectrophotometric assay in which the oxidation of NADPH was measured [Thelander78].


Enzymatic reaction of: GDP reductase (ribonucleoside diphosphate reductase 1)

EC Number: 1.17.4.1

dGDP + an oxidized thioredoxin + H2O <=> GDP + a reduced thioredoxin

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: superpathway of histidine, purine, and pyrimidine biosynthesis , superpathway of purine nucleotides de novo biosynthesis II , superpathway of guanosine nucleotides de novo biosynthesis II , guanosine deoxyribonucleotides de novo biosynthesis II

Summary:
Glutaredoxin may substitute for thioredoxin in the reaction.

The reduction of GDP by purified enzyme from Escherichia coli strain KK546 has been shown using a coupled spectrophotometric assay in which the oxidation of NADPH was measured [Thelander78].


Subunit of ribonucleoside diphosphate reductase 1: ribonucleoside diphosphate reductase 1, α subunit dimer

Synonyms: dnaF, R1 protein, B1 protein

Gene: nrdA Accession Numbers: EG10660 (EcoCyc), b2234, ECK2226

Locations: cytosol

Subunit composition of ribonucleoside diphosphate reductase 1, α subunit dimer = [NrdA]2
         ribonucleoside diphosphate reductase 1, α subunit = NrdA

Map Position: [2,342,887 -> 2,345,172] (50.5 centisomes)
Length: 2286 bp / 761 aa

Molecular Weight of Polypeptide: 85.775 kD (from nucleotide sequence)

pI: 5.97

GO Terms:

Biological Process: GO:0009263 - deoxyribonucleotide biosynthetic process Inferred from experiment [Reichard62]
GO:0015949 - nucleobase-containing small molecule interconversion Inferred from experiment [Reichard62]
GO:0006260 - DNA replication Inferred by computational analysis [UniProtGOA12, UniProtGOA11a, GOA01a]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0004748 - ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Thelander78]
GO:0005524 - ATP binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Brown69a]
GO:0042803 - protein homodimerization activity Inferred from experiment [Thelander73]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11a]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]
GO:0005971 - ribonucleoside-diphosphate reductase complex Inferred from experiment [Reichard62]

MultiFun Terms: metabolism central intermediary metabolism nucleotide and nucleoside conversions

Unification Links: DIP:DIP-584N , EcoliWiki:b2234 , Mint:MINT-1233906 , ModBase:P00452 , PR:PRO_000023402 , Pride:P00452 , Protein Model Portal:P00452 , RefSeq:NP_416737 , SMR:P00452 , String:511145.b2234 , UniProt:P00452

Relationship Links: InterPro:IN-FAMILY:IPR000788 , InterPro:IN-FAMILY:IPR005144 , InterPro:IN-FAMILY:IPR008926 , InterPro:IN-FAMILY:IPR013346 , InterPro:IN-FAMILY:IPR013509 , PDB:Structure:1QFN , PDB:Structure:1R1R , PDB:Structure:1RLR , PDB:Structure:2R1R , PDB:Structure:2X0X , PDB:Structure:2XAK , PDB:Structure:2XAP , PDB:Structure:2XAV , PDB:Structure:2XAW , PDB:Structure:2XAX , PDB:Structure:2XAY , PDB:Structure:2XAZ , PDB:Structure:2XO4 , PDB:Structure:2XO5 , PDB:Structure:3R1R , PDB:Structure:3UUS , PDB:Structure:4ERM , PDB:Structure:4ERP , PDB:Structure:4R1R , PDB:Structure:5R1R , PDB:Structure:6R1R , PDB:Structure:7R1R , Pfam:IN-FAMILY:PF00317 , Pfam:IN-FAMILY:PF02867 , Pfam:IN-FAMILY:PF03477 , Prints:IN-FAMILY:PR01183 , Prosite:IN-FAMILY:PS00089 , Prosite:IN-FAMILY:PS51161

Summary:
The B1 protein of ribonucleoside-diphosphate reductase consists of two polypeptide chains of similar or identical size. Both polypeptides have isoleucine as the COOH-terminal residue, however the NH2-terminals are different, one has glutamic acid, the other aspartic acid [Thelander73]. The B1 protein contains the binding sites for the allosteric effectors as well as the binding sites for the ribonucleoside diphosphate substrates. There are two substrate binding sites per B1 molecule and they are distinct from the effector binding sites. [Thelander78]

NrdA and/or NrdB are required for growth of a nrdD or nrdG null mutant under microaerophilic conditions [Garriga96].

Mutants with partial disruption of NrdA function have a greater number of double-strand breaks caused by replication fork stalling than in wild type cells, although apparently not due to a lack of deoxyribonucleotides [Guarino07].

Review: [Kolberg04]

Gene Citations: [Jordan96]

Essentiality data for nrdA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 2]

Subunit of ribonucleoside diphosphate reductase 1: ribonucleoside diphosphate reductase 1, β subunit dimer

Synonyms: ftsB, R2 protein, B2 protein

Gene: nrdB Accession Numbers: EG10661 (EcoCyc), b2235, ECK2227

Locations: cytosol

Subunit composition of ribonucleoside diphosphate reductase 1, β subunit dimer = [NrdB]2
         ribonucleoside diphosphate reductase 1, β subunit, ferritin-like = NrdB

Map Position: [2,345,406 -> 2,346,536] (50.55 centisomes)
Length: 1131 bp / 376 aa

Molecular Weight of Polypeptide: 43.517 kD (from nucleotide sequence)

pI: 4.9

GO Terms:

Biological Process: GO:0009263 - deoxyribonucleotide biosynthetic process Inferred from experiment [Reichard62]
GO:0015949 - nucleobase-containing small molecule interconversion Inferred from experiment [Brown69a]
GO:0006260 - DNA replication Inferred by computational analysis [UniProtGOA12, UniProtGOA11a]
GO:0009186 - deoxyribonucleoside diphosphate metabolic process Inferred by computational analysis [GOA01a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0005506 - iron ion binding Inferred from experiment [Hristova08]
GO:0042802 - identical protein binding Inferred from experiment [Lasserre06, Rajagopala09]
GO:0042803 - protein homodimerization activity Inferred from experiment [Thelander73]
GO:0004748 - ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred by computational analysis [GOA01]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred from experiment [Reichard62]
GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, Watt07, Lasserre06]
GO:0005971 - ribonucleoside-diphosphate reductase complex Inferred from experiment [Reichard62]

MultiFun Terms: metabolism central intermediary metabolism nucleotide and nucleoside conversions

Unification Links: DIP:DIP-36213N , DisProt:DP00107 , EcoliWiki:b2235 , Mint:MINT-1269534 , PR:PRO_000023403 , Pride:P69924 , Protein Model Portal:P69924 , RefSeq:NP_416738 , SMR:P69924 , String:511145.b2235 , UniProt:P69924

Relationship Links: InterPro:IN-FAMILY:IPR000358 , InterPro:IN-FAMILY:IPR009078 , InterPro:IN-FAMILY:IPR012348 , Panther:IN-FAMILY:PTHR23409 , PDB:Structure:1AV8 , PDB:Structure:1BIQ , PDB:Structure:1JPR , PDB:Structure:1JQC , PDB:Structure:1MRR , PDB:Structure:1MXR , PDB:Structure:1PFR , PDB:Structure:1PIM , PDB:Structure:1PIU , PDB:Structure:1PIY , PDB:Structure:1PIZ , PDB:Structure:1PJ0 , PDB:Structure:1PJ1 , PDB:Structure:1PM2 , PDB:Structure:1R1R , PDB:Structure:1R65 , PDB:Structure:1RIB , PDB:Structure:1RNR , PDB:Structure:1RSR , PDB:Structure:1RSV , PDB:Structure:1XIK , PDB:Structure:1YFD , PDB:Structure:2ALX , PDB:Structure:2AV8 , PDB:Structure:2R1R , PDB:Structure:2X0X , PDB:Structure:2XAK , PDB:Structure:2XAP , PDB:Structure:2XAV , PDB:Structure:2XAW , PDB:Structure:2XAX , PDB:Structure:2XAY , PDB:Structure:2XAZ , PDB:Structure:2XO4 , PDB:Structure:2XO5 , PDB:Structure:2XOF , PDB:Structure:3R1R , PDB:Structure:3UUS , PDB:Structure:4ERM , PDB:Structure:4ERP , PDB:Structure:4R1R , PDB:Structure:5R1R , PDB:Structure:6R1R , PDB:Structure:7R1R , Pfam:IN-FAMILY:PF00268 , Prosite:IN-FAMILY:PS00368

Summary:
The B2 protein of ribonucleoside-diphosphate reductase contains the tyrosyl radical-dinuclear iron center, which is thought to initiate catalysis by long-range electron transfer. [Mao92, Thelander73]

NrdA and/or NrdB are required for growth of a nrdD or nrdG null mutant under microaerophilic conditions [Garriga96].

Review: [Kolberg04]

Gene Citations: [Jordan96]

Essentiality data for nrdB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox No 37 Aerobic 7   No [Baba06, Comment 2]

References

Allard92: Allard P, Kuprin S, Shen B, Ehrenberg A (1992). "Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase from Escherichia coli studied by 1H NMR. Different properties of the large protein subunit and the holoenzyme." Eur J Biochem 1992;208(3);635-42. PMID: 1396671

Andersson99: Andersson ME, Hogbom M, Rinaldo-Matthis A, Andersson KK, Sjoberg BM, Nordlund P (1999). "The Crystal Structure of an Azide Complex of the Diferrous R2 Subunit of Ribonucleotide Reductase Displays a Novel Carboxylate Shift with Important Mechanistic Implications for Diiron-Catalyzed Oxygen Activation." J. Am. Chem. Soc. 121: 2346-2352.

Artin09: Artin E, Wang J, Lohman GJ, Yokoyama K, Yu G, Griffin RG, Bar G, Stubbe J (2009). "Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5'-diphosphate in the presence or absence of reductant." Biochemistry 48(49);11622-9. PMID: 19899770

Assarsson01: Assarsson M, Andersson ME, Hogbom M, Persson BO, Sahlin M, Barra AL, Sjoberg BM, Nordlund P, Graslund A (2001). "Restoring proper radical generation by azide binding to the iron site of the E238A mutant R2 protein of ribonucleotide reductase from Escherichia coli." J Biol Chem 276(29);26852-9. PMID: 11328804

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Berardi99: Berardi MJ, Bushweller JH (1999). "Binding specificity and mechanistic insight into glutaredoxin-catalyzed protein disulfide reduction." J Mol Biol 292(1);151-61. PMID: 10493864

Brignole12: Brignole EJ, Ando N, Zimanyi CM, Drennan CL (2012). "The prototypic class Ia ribonucleotide reductase from Escherichia coli: still surprising after all these years." Biochem Soc Trans 40(3);523-30. PMID: 22616862

Brown69: Brown NC, Canellakis ZN, Lundin B, Reichard P, Thelander L (1969). "Ribonucleoside diphosphate reductase. Purification of the two subunits, proteins B1 and B2." Eur J Biochem 1969;9(4);561-73. PMID: 4896737

Brown69a: Brown NC, Reichard P (1969). "Ribonucleoside diphosphate reductase. Formation of active and inactive complexes of proteins B1 and B2." J Mol Biol 46(1);25-38. PMID: 4902211

Casado91: Casado C, Llagostera M, Barbe J (1991). "Expression of nrdA and nrdB genes of Escherichia coli is decreased under anaerobiosis." FEMS Microbiol Lett 1991;67(2);153-7. PMID: 1778429

Coves95: Coves J, Delon B, Climent I, Sjoberg BM, Fontecave M (1995). "Enzymic and chemical reduction of the iron center of the Escherichia coli ribonucleotide reductase protein R2. The role of the C-terminus." Eur J Biochem 1995;233(1);357-63. PMID: 7588767

Crona10: Crona M, Furrer E, Torrents E, Edgell DR, Sjoberg BM (2010). "Subunit and small-molecule interaction of ribonucleotide reductases via surface plasmon resonance biosensor analyses." Protein Eng Des Sel 23(8);633-41. PMID: 20534631

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Feeney11: Feeney MA, Veeravalli K, Boyd D, Gon S, Faulkner MJ, Georgiou G, Beckwith J (2011). "Repurposing lipoic acid changes electron flow in two important metabolic pathways of Escherichia coli." Proc Natl Acad Sci U S A 108(19);7991-6. PMID: 21521794

Filpula77: Filpula D, Fuchs JA (1977). "Regulation of ribonucleoside diphosphate reductase synthesis in Escherichia coli: increased enzyme synthesis as a result of inhibition of deoxyribonucleic acid synthesis." J Bacteriol 130(1);107-13. PMID: 67110

Garriga96: Garriga X, Eliasson R, Torrents E, Jordan A, Barbe J, Gibert I, Reichard P (1996). "nrdD and nrdG genes are essential for strict anaerobic growth of Escherichia coli." Biochem Biophys Res Commun 1996;229(1);189-92. PMID: 8954104

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Gon06: Gon S, Faulkner MJ, Beckwith J (2006). "In vivo requirement for glutaredoxins and thioredoxins in the reduction of the ribonucleotide reductases of Escherichia coli." Antioxid Redox Signal 8(5-6);735-42. PMID: 16771665

Gon11: Gon S, Napolitano R, Rocha W, Coulon S, Fuchs RP (2011). "Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in Escherichia coli." Proc Natl Acad Sci U S A 108(48);19311-6. PMID: 22084087

Guarino07: Guarino E, Jimenez-Sanchez A, Guzman EC (2007). "Defective ribonucleoside diphosphate reductase impairs replication fork progression in Escherichia coli." J Bacteriol 189(9):3496-501. PMID: 17322311

Guittet00: Guittet O, Decottignies P, Serani L, Henry Y, Le Marechal P, Laprevote O, Lepoivre M (2000). "Peroxynitrite-mediated nitration of the stable free radical tyrosine residue of the ribonucleotide reductase small subunit." Biochemistry 2000;39(16);4640-8. PMID: 10769119

Hassan08: Hassan AQ, Wang Y, Plate L, Stubbe J (2008). "Methodology to probe subunit interactions in ribonucleotide reductases." Biochemistry 47(49);13046-55. PMID: 19012414

Helmward89: Helmward Z "Handbook of Enzyme Inhibitors. 2nd, revised and enlarged edition." Weinheim, Federal Republic of Germany ; New York, NY, USA , 1989.

Hogbom03: Hogbom M, Galander M, Andersson M, Kolberg M, Hofbauer W, Lassmann G, Nordlund P, Lendzian F (2003). "Displacement of the tyrosyl radical cofactor in ribonucleotide reductase obtained by single-crystal high-field EPR and 1.4-A x-ray data." Proc Natl Acad Sci U S A 100(6);3209-14. PMID: 12624184

Hristova08: Hristova D, Wu CH, Jiang W, Krebs C, Stubbe J (2008). "Importance of the maintenance pathway in the regulation of the activity of Escherichia coli ribonucleotide reductase." Biochemistry 47(13):3989-99. PMID: 18314964

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jordan96: Jordan A, Aragall E, Gibert I, Barbe J (1996). "Promoter identification and expression analysis of Salmonella typhimurium and Escherichia coli nrdEF operons encoding one of two class I ribonucleotide reductases present in both bacteria." Mol Microbiol 19(4);777-90. PMID: 8820648

Kolberg04: Kolberg M, Strand KR, Graff P, Andersson KK (2004). "Structure, function, and mechanism of ribonucleotide reductases." Biochim Biophys Acta 1699(1-2);1-34. PMID: 15158709

Kolberg05: Kolberg M, Logan DT, Bleifuss G, Potsch S, Sjoberg BM, Graslund A, Lubitz W, Lassmann G, Lendzian F (2005). "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(12);11233-46. PMID: 15634667

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Mao92: Mao SS, Yu GX, Chalfoun D, Stubbe J (1992). "Characterization of C439SR1, a mutant of Escherichia coli ribonucleotide diphosphate reductase: evidence that C439 is a residue essential for nucleotide reduction and C439SR1 is a protein possessing novel thioredoxin-like activity." Biochemistry 1992;31(40);9752-9. PMID: 1390751

Martin11: Martin JE, Imlay JA (2011). "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(2);319-34. PMID: 21338418

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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