Escherichia coli K-12 substr. MG1655 Protein: oxidized ribonucleoside-triphosphate reductase

Gene: nrdD Accession Numbers: EG11417 (EcoCyc), b4238, ECK4233

Regulation Summary Diagram: ?

Regulation summary diagram for nrdD

Subunit composition of ribonucleoside-triphosphate reductase = [NrdD]2
         ribonucleoside-triphosphate reductase = NrdD

Alternative forms of oxidized ribonucleoside-triphosphate reductase: ribonucleoside-triphosphate reductase

Gene Citations: [Garriga96]

Map Position: [4,458,545 <- 4,460,683] (96.1 centisomes, 346°)
Length: 2139 bp / 712 aa

Unification Links: ASAP:ABE-0013865 , CGSC:34589 , EchoBASE:EB1388 , EcoGene:EG11417 , OU-Microarray:b4238 , PortEco:nrdD , RegulonDB:EG11417

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for nrdD

MultiFun Terms: metabolism central intermediary metabolism 2'-deoxyribonucleotide metabolism

Created 02-Oct-2008 by Shearer A , SRI International

Subunit of oxidized ribonucleoside-triphosphate reductase: ribonucleoside-triphosphate reductase

Synonyms: NrdD

Gene: nrdD Accession Numbers: EG11417 (EcoCyc), b4238, ECK4233

Locations: cytosol

Sequence Length: 712 AAs

Molecular Weight: 80.023 kD (from nucleotide sequence)

pI: 6.87

GO Terms:

Biological Process: GO:0015949 - nucleobase-containing small molecule interconversion Inferred from experiment [Garriga96]
GO:0006260 - DNA replication Inferred by computational analysis [GOA01]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0008270 - zinc ion binding Inferred from experiment [Luttringer09]
GO:0008998 - ribonucleoside-triphosphate reductase activity Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Eliasson94]
GO:0042803 - protein homodimerization activity Inferred from experiment [Eliasson92]
GO:0051065 - CTP reductase activity Inferred from experiment [Eliasson92]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0031250 - anaerobic ribonucleoside-triphosphate reductase complex Inferred from experiment [Garriga96]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism central intermediary metabolism 2'-deoxyribonucleotide metabolism

Unification Links: DIP:DIP-10358N , EcoliWiki:b4238 , ModBase:P28903 , Pride:P28903 , Protein Model Portal:P28903 , RefSeq:NP_418659 , SMR:P28903 , String:511145.b4238 , Swiss-Model:P28903 , UniProt:P28903

Relationship Links: InterPro:IN-FAMILY:IPR001150 , InterPro:IN-FAMILY:IPR005144 , InterPro:IN-FAMILY:IPR012833 , InterPro:IN-FAMILY:IPR019777 , Pfam:IN-FAMILY:PF03477 , Prosite:IN-FAMILY:PS00850 , Prosite:IN-FAMILY:PS51149 , Prosite:IN-FAMILY:PS51161

The NrdD reductase is activated by the NrdG activase under anaerobic conditions and is inactivated by oxygen. The protein is highly sensitive to O2.

An nrdD null mutant does not grow under entirely anaerobic conditions, but grows under aerobic or microaerophilic conditions due to the activity of NrdA and/or NrdB [Garriga96].

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 III ribonucleotide reductase that is essential for anaerobic growth. In E. coli strain DHB4, construction of deletion mutants and analysis of their growth characteristics showed that the main ribonucleotide reductase activity in strict anaerobiosis is provided by the products of genes nrdD and nrdG. Under highly restricted oxygen condtions, the products of genes nrdA and nrdB can support some growth in a strain containing a deletion of nrdD and nrdG. Either thioredoxin reductase or glutathione reductase are required for anaerobic growth, suggesting that these reductive pathways contribute to enzyme activity [Gon06].

Essentiality data for nrdD knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b4238 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11417; confirmed by SwissProt match.


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

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

Eliasson92: Eliasson R, Pontis E, Fontecave M, Gerez C, Harder J, Jornvall H, Krook M, Reichard P (1992). "Characterization of components of the anaerobic ribonucleotide reductase system from Escherichia coli." J Biol Chem 267(35);25541-7. PMID: 1460049

Eliasson94: Eliasson R, Pontis E, Sun X, Reichard P (1994). "Allosteric control of the substrate specificity of the anaerobic ribonucleotide reductase from Escherichia coli." J Biol Chem 269(42);26052-7. PMID: 7929317

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

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

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Luttringer09: Luttringer F, Mulliez E, Dublet B, Lemaire D, Fontecave M (2009). "The Zn center of the anaerobic ribonucleotide reductase from E. coli." J Biol Inorg Chem 14(6);923-33. PMID: 19381696

Torrents07: Torrents E, Grinberg I, Gorovitz-Harris B, Lundstrom H, Borovok I, Aharonowitz Y, Sjoberg BM, Cohen G (2007). "NrdR controls differential expression of the Escherichia coli ribonucleotide reductase genes." J Bacteriol 189(14);5012-21. PMID: 17496099

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Other References Related to Gene Regulation

Boston03: Boston T, Atlung T (2003). "FNR-mediated oxygen-responsive regulation of the nrdDG operon of Escherichia coli." J Bacteriol 185(17);5310-3. PMID: 12923108

Cendra13: Cendra Mdel M, Juarez A, Madrid C, Torrents E (2013). "H-NS is a novel transcriptional modulator of the ribonucleotide reductase genes in Escherichia coli." J Bacteriol 195(18);4255-63. PMID: 23873909

Roca08: Roca I, Ballana E, Panosa A, Torrents E, Gibert I (2008). "Fumarate and nitrate reduction (FNR) dependent activation of the Escherichia coli anaerobic ribonucleotide reductase nrdDG promoter." Int Microbiol 11(1);49-56. PMID: 18683632

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Fri Oct 9, 2015, BIOCYC11A.