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Protein

Ribonucleoside-diphosphate reductase 1 subunit alpha

Gene

nrdA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. R1 contains the binding sites for both substrates and allosteric effectors and carries out the actual reduction of the ribonucleotide. It also provides redox-active cysteines.

Catalytic activityi

2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.

Enzyme regulationi

Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the alpha subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site. In vitro, its activity is increased by dithiothreitol (DTT) or thioredoxins (non-specific). Inhibited by hydroxyurea, leads to dNTP depletion, replication fork arrest and genomic instability (PubMed:20005847).1 Publication2 Publications

Pathwayi: DNA replication

This protein is involved in the pathway DNA replication, which is part of Genetic information processing.
View all proteins of this organism that are known to be involved in the pathway DNA replication and in Genetic information processing.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei9Allosteric activator1
Binding sitei55Allosteric activator1
Binding sitei91Allosteric activator1
Binding sitei209Substrate1
Sitei225Important for hydrogen atom transfer1
Sitei232Allosteric effector binding1
Binding sitei253Substrate; via amide nitrogenBy similarity1
Sitei262Allosteric effector binding1
Active sitei437Proton acceptor1
Active sitei439Cysteine radical intermediate1
Active sitei441Proton acceptor1
Sitei462Important for hydrogen atom transfer1
Sitei730Important for electron transfer1
Sitei731Important for electron transfer1
Sitei754Interacts with thioredoxin/glutaredoxin1
Sitei759Interacts with thioredoxin/glutaredoxin1

GO - Molecular functioni

  • ATP binding Source: EcoliWiki
  • ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Source: EcoCyc

GO - Biological processi

  • deoxyribonucleotide biosynthetic process Source: EcoliWiki
  • DNA replication Source: UniProtKB-UniPathway
  • nucleobase-containing small molecule interconversion Source: EcoliWiki
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

DNA replication

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:NRDA-MONOMER.
ECOL316407:JW2228-MONOMER.
MetaCyc:NRDA-MONOMER.
BRENDAi1.17.4.1. 2026.
SABIO-RKP00452.
UniPathwayiUPA00326.

Names & Taxonomyi

Protein namesi
Recommended name:
Ribonucleoside-diphosphate reductase 1 subunit alpha (EC:1.17.4.1)
Alternative name(s):
Protein B1
Ribonucleoside-diphosphate reductase 1 R1 subunit
Ribonucleotide reductase 1
Gene namesi
Name:nrdA
Synonyms:dnaF
Ordered Locus Names:b2234, JW2228
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10660. nrdA.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: EcoCyc
  • ribonucleoside-diphosphate reductase complex Source: EcoliWiki
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi441E → A or Q: Loss of activity. 1 Publication1
Mutagenesisi441E → D: Decrease in activity. 1 Publication1
Mutagenesisi730Y → F: Loss of activity. 1 Publication1
Mutagenesisi731Y → F: Loss of activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000305961 – 761Ribonucleoside-diphosphate reductase 1 subunit alphaAdd BLAST761

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi225 ↔ 462Redox-active2 Publications
Modified residuei283N6-acetyllysine1 Publication1

Post-translational modificationi

Binding of the substrate occurs primarily when the active-site cysteines are reduced.

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

EPDiP00452.
PaxDbiP00452.
PRIDEiP00452.

Expressioni

Inductioni

Induced 5-fold by hydroxyurea (at protein level).1 Publication

Interactioni

Subunit structurei

Tetramer of two alpha (R1) and two beta (R2) subunits. The B1 protein is a dimer of alpha subunits. A radical transfer pathway occurs between 'Tyr-122' of R2 and R1.2 Publications

Protein-protein interaction databases

BioGridi4262130. 181 interactors.
DIPiDIP-584N.
IntActiP00452. 9 interactors.
MINTiMINT-1233906.
STRINGi511145.b2234.

Structurei

Secondary structure

1761
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 8Combined sources3
Beta strandi10 – 12Combined sources3
Beta strandi14 – 16Combined sources3
Helixi19 – 30Combined sources12
Helixi38 – 46Combined sources9
Helixi55 – 68Combined sources14
Beta strandi72 – 74Combined sources3
Helixi77 – 94Combined sources18
Beta strandi95 – 98Combined sources4
Helixi102 – 111Combined sources10
Helixi118 – 122Combined sources5
Helixi125 – 134Combined sources10
Helixi137 – 142Combined sources6
Helixi145 – 154Combined sources10
Turni160 – 162Combined sources3
Helixi169 – 180Combined sources12
Turni181 – 183Combined sources3
Turni186 – 188Combined sources3
Helixi189 – 201Combined sources13
Beta strandi204 – 206Combined sources3
Helixi209 – 214Combined sources6
Beta strandi217 – 219Combined sources3
Beta strandi225 – 229Combined sources5
Helixi234 – 248Combined sources15
Turni249 – 251Combined sources3
Beta strandi253 – 257Combined sources5
Beta strandi268 – 271Combined sources4
Helixi274 – 276Combined sources3
Helixi278 – 289Combined sources12
Turni290 – 292Combined sources3
Beta strandi296 – 299Combined sources4
Beta strandi301 – 307Combined sources7
Helixi313 – 317Combined sources5
Turni318 – 320Combined sources3
Beta strandi322 – 324Combined sources3
Helixi326 – 328Combined sources3
Beta strandi333 – 339Combined sources7
Helixi341 – 349Combined sources9
Beta strandi352 – 356Combined sources5
Helixi358 – 360Combined sources3
Helixi364 – 370Combined sources7
Helixi372 – 384Combined sources13
Beta strandi386 – 388Combined sources3
Beta strandi391 – 394Combined sources4
Helixi395 – 409Combined sources15
Beta strandi412 – 416Combined sources5
Helixi419 – 422Combined sources4
Beta strandi423 – 426Combined sources4
Turni428 – 430Combined sources3
Beta strandi438 – 440Combined sources3
Beta strandi463 – 468Combined sources6
Turni469 – 471Combined sources3
Helixi475 – 477Combined sources3
Helixi478 – 495Combined sources18
Helixi501 – 510Combined sources10
Beta strandi513 – 518Combined sources6
Helixi520 – 526Combined sources7
Beta strandi531 – 534Combined sources4
Helixi537 – 562Combined sources26
Helixi568 – 570Combined sources3
Helixi573 – 575Combined sources3
Helixi579 – 582Combined sources4
Helixi585 – 589Combined sources5
Helixi599 – 609Combined sources11
Beta strandi612 – 614Combined sources3
Helixi624 – 628Combined sources5
Beta strandi639 – 645Combined sources7
Beta strandi648 – 650Combined sources3
Beta strandi652 – 655Combined sources4
Helixi659 – 662Combined sources4
Turni663 – 665Combined sources3
Helixi669 – 671Combined sources3
Beta strandi672 – 675Combined sources4
Helixi676 – 686Combined sources11
Beta strandi697 – 699Combined sources3
Helixi701 – 703Combined sources3
Helixi705 – 707Combined sources3
Helixi711 – 723Combined sources13
Beta strandi732 – 734Combined sources3
Helixi738 – 741Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QFNNMR-B737-761[»]
1R1RX-ray2.90A/B/C1-761[»]
1RLRX-ray2.50A1-761[»]
2R1RX-ray3.00A/B/C1-761[»]
2X0XX-ray2.30A/B/C1-761[»]
2XAKX-ray2.80A/B/C1-761[»]
2XAPX-ray2.10A/B/C1-761[»]
2XAVX-ray2.80A/B/C1-761[»]
2XAWX-ray3.10A/B/C1-761[»]
2XAXX-ray2.75A/B/C1-761[»]
2XAYX-ray2.65A/B/C1-761[»]
2XAZX-ray2.60A/B/C1-761[»]
2XO4X-ray2.50A/B/C1-761[»]
2XO5X-ray2.70A/B/C1-761[»]
3R1RX-ray3.00A/B/C1-761[»]
3UUSX-ray5.65A/B/C/D1-761[»]
4ERMX-ray3.95A/B/C/D1-761[»]
4ERPX-ray4.45A/B/C/D1-761[»]
4R1RX-ray3.20A/B/C1-761[»]
5CNSX-ray2.98A/B/C/D1-761[»]
5CNTX-ray3.25A/B/C/D1-761[»]
5CNUX-ray3.40A/B/C/D1-761[»]
5CNVX-ray3.20A/B/C/D1-761[»]
5R1RX-ray3.10A/B/C1-761[»]
6R1RX-ray3.10A/B/C1-761[»]
7R1RX-ray3.10A/B/C1-761[»]
ProteinModelPortaliP00452.
SMRiP00452.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00452.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 95ATP-conePROSITE-ProRule annotationAdd BLAST91

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 21Allosteric activator binding7
Regioni224 – 225Substrate bindingBy similarity2
Regioni437 – 441Substrate bindingBy similarity5
Regioni621 – 625Substrate binding5

Sequence similaritiesi

Contains 1 ATP-cone domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG4105BZH. Bacteria.
COG0209. LUCA.
HOGENOMiHOG000278076.
InParanoidiP00452.
KOiK00525.
OMAiYELLWQM.
PhylomeDBiP00452.

Family and domain databases

InterProiIPR005144. ATP-cone_dom.
IPR013346. NrdE_NrdA.
IPR000788. RNR_lg_C.
IPR013509. RNR_lsu_N.
IPR008926. RNR_R1-su_N.
[Graphical view]
PfamiPF03477. ATP-cone. 1 hit.
PF02867. Ribonuc_red_lgC. 1 hit.
PF00317. Ribonuc_red_lgN. 1 hit.
[Graphical view]
PRINTSiPR01183. RIBORDTASEM1.
SUPFAMiSSF48168. SSF48168. 1 hit.
TIGRFAMsiTIGR02506. NrdE_NrdA. 1 hit.
PROSITEiPS51161. ATP_CONE. 1 hit.
PS00089. RIBORED_LARGE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform Alpha (identifier: P00452-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNQNLLVTKR DGSTERINLD KIHRVLDWAA EGLHNVSISQ VELRSHIQFY
60 70 80 90 100
DGIKTSDIHE TIIKAAADLI SRDAPDYQYL AARLAIFHLR KKAYGQFEPP
110 120 130 140 150
ALYDHVVKMV EMGKYDNHLL EDYTEEEFKQ MDTFIDHDRD MTFSYAAVKQ
160 170 180 190 200
LEGKYLVQNR VTGEIYESAQ FLYILVAACL FSNYPRETRL QYVKRFYDAV
210 220 230 240 250
STFKISLPTP IMSGVRTPTR QFSSCVLIEC GDSLDSINAT SSAIVKYVSQ
260 270 280 290 300
RAGIGINAGR IRALGSPIRG GEAFHTGCIP FYKHFQTAVK SCSQGGVRGG
310 320 330 340 350
AATLFYPMWH LEVESLLVLK NNRGVEGNRV RHMDYGVQIN KLMYTRLLKG
360 370 380 390 400
EDITLFSPSD VPGLYDAFFA DQEEFERLYT KYEKDDSIRK QRVKAVELFS
410 420 430 440 450
LMMQERASTG RIYIQNVDHC NTHSPFDPAI APVRQSNLCL EIALPTKPLN
460 470 480 490 500
DVNDENGEIA LCTLSAFNLG AINNLDELEE LAILAVRALD ALLDYQDYPI
510 520 530 540 550
PAAKRGAMGR RTLGIGVINF AYYLAKHGKR YSDGSANNLT HKTFEAIQYY
560 570 580 590 600
LLKASNELAK EQGACPWFNE TTYAKGILPI DTYKKDLDTI ANEPLHYDWE
610 620 630 640 650
ALRESIKTHG LRNSTLSALM PSETSSQISN ATNGIEPPRG YVSIKASKDG
660 670 680 690 700
ILRQVVPDYE HLHDAYELLW EMPGNDGYLQ LVGIMQKFID QSISANTNYD
710 720 730 740 750
PSRFPSGKVP MQQLLKDLLT AYKFGVKTLY YQNTRDGAED AQDDLVPSIQ
760
DDGCESGACK I
Length:761
Mass (Da):85,775
Last modified:November 1, 1997 - v2
Checksum:i7E034F154567C3FC
GO
Isoform Alpha' (identifier: P00452-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.
     26-26: L → M

Show »
Length:736
Mass (Da):82,860
Checksum:i498ADEDC2154C084
GO

Sequence cautioni

The sequence AAA24223 differs from that shown.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti1 – 2Missing in 15% of the chains. 2
Natural varianti1Missing in 30% of the chains. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0188711 – 25Missing in isoform Alpha'. CuratedAdd BLAST25
Alternative sequenceiVSP_01887226L → M in isoform Alpha'. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02672 Genomic DNA. Translation: AAA24223.1. Sequence problems.
X06999 Genomic DNA. Translation: CAA30056.2.
U00096 Genomic DNA. Translation: AAC75294.1.
AP009048 Genomic DNA. Translation: BAA16053.1.
PIRiH64993. RDEC1R.
RefSeqiNP_416737.1. NC_000913.3.
WP_001075164.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC75294; AAC75294; b2234.
BAA16053; BAA16053; BAA16053.
GeneIDi946612.
KEGGiecj:JW2228.
eco:b2234.
PATRICi32119827. VBIEscCol129921_2323.

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02672 Genomic DNA. Translation: AAA24223.1. Sequence problems.
X06999 Genomic DNA. Translation: CAA30056.2.
U00096 Genomic DNA. Translation: AAC75294.1.
AP009048 Genomic DNA. Translation: BAA16053.1.
PIRiH64993. RDEC1R.
RefSeqiNP_416737.1. NC_000913.3.
WP_001075164.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1QFNNMR-B737-761[»]
1R1RX-ray2.90A/B/C1-761[»]
1RLRX-ray2.50A1-761[»]
2R1RX-ray3.00A/B/C1-761[»]
2X0XX-ray2.30A/B/C1-761[»]
2XAKX-ray2.80A/B/C1-761[»]
2XAPX-ray2.10A/B/C1-761[»]
2XAVX-ray2.80A/B/C1-761[»]
2XAWX-ray3.10A/B/C1-761[»]
2XAXX-ray2.75A/B/C1-761[»]
2XAYX-ray2.65A/B/C1-761[»]
2XAZX-ray2.60A/B/C1-761[»]
2XO4X-ray2.50A/B/C1-761[»]
2XO5X-ray2.70A/B/C1-761[»]
3R1RX-ray3.00A/B/C1-761[»]
3UUSX-ray5.65A/B/C/D1-761[»]
4ERMX-ray3.95A/B/C/D1-761[»]
4ERPX-ray4.45A/B/C/D1-761[»]
4R1RX-ray3.20A/B/C1-761[»]
5CNSX-ray2.98A/B/C/D1-761[»]
5CNTX-ray3.25A/B/C/D1-761[»]
5CNUX-ray3.40A/B/C/D1-761[»]
5CNVX-ray3.20A/B/C/D1-761[»]
5R1RX-ray3.10A/B/C1-761[»]
6R1RX-ray3.10A/B/C1-761[»]
7R1RX-ray3.10A/B/C1-761[»]
ProteinModelPortaliP00452.
SMRiP00452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262130. 181 interactors.
DIPiDIP-584N.
IntActiP00452. 9 interactors.
MINTiMINT-1233906.
STRINGi511145.b2234.

Proteomic databases

EPDiP00452.
PaxDbiP00452.
PRIDEiP00452.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC75294; AAC75294; b2234.
BAA16053; BAA16053; BAA16053.
GeneIDi946612.
KEGGiecj:JW2228.
eco:b2234.
PATRICi32119827. VBIEscCol129921_2323.

Organism-specific databases

EchoBASEiEB0654.
EcoGeneiEG10660. nrdA.

Phylogenomic databases

eggNOGiENOG4105BZH. Bacteria.
COG0209. LUCA.
HOGENOMiHOG000278076.
InParanoidiP00452.
KOiK00525.
OMAiYELLWQM.
PhylomeDBiP00452.

Enzyme and pathway databases

UniPathwayiUPA00326.
BioCyciEcoCyc:NRDA-MONOMER.
ECOL316407:JW2228-MONOMER.
MetaCyc:NRDA-MONOMER.
BRENDAi1.17.4.1. 2026.
SABIO-RKP00452.

Miscellaneous databases

EvolutionaryTraceiP00452.
PROiP00452.

Family and domain databases

InterProiIPR005144. ATP-cone_dom.
IPR013346. NrdE_NrdA.
IPR000788. RNR_lg_C.
IPR013509. RNR_lsu_N.
IPR008926. RNR_R1-su_N.
[Graphical view]
PfamiPF03477. ATP-cone. 1 hit.
PF02867. Ribonuc_red_lgC. 1 hit.
PF00317. Ribonuc_red_lgN. 1 hit.
[Graphical view]
PRINTSiPR01183. RIBORDTASEM1.
SUPFAMiSSF48168. SSF48168. 1 hit.
TIGRFAMsiTIGR02506. NrdE_NrdA. 1 hit.
PROSITEiPS51161. ATP_CONE. 1 hit.
PS00089. RIBORED_LARGE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRIR1_ECOLI
AccessioniPrimary (citable) accession number: P00452
Secondary accession number(s): P78088, P78177
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 175 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

E.coli produces two separate class I enzymes. This one is the functional enzyme during growth.
Two distinct regulatory sites have been defined: one controls substrate specificity and the other regulates the overall catalytic activity. A substrate-binding catalytic site, located on R1, is formed only in the presence of the second subunit R2.

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.