ID   RIR3_ECOLI              Reviewed;         714 AA.
AC   P39452; P78101; P78210; P78211; Q59417;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=Ribonucleoside-diphosphate reductase 2 subunit alpha;
DE            EC=1.17.4.1;
DE   AltName: Full=R1E protein;
DE   AltName: Full=Ribonucleotide reductase 2;
GN   Name=nrdE; OrderedLocusNames=b2675, JW2650;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=9205837; DOI=10.1093/dnares/4.2.91;
RA   Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T.,
RA   Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K.,
RA   Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T., Oyama S.,
RA   Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H.,
RA   Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.;
RT   "Construction of a contiguous 874-kb sequence of the Escherichia coli-K12
RT   genome corresponding to 50.0-68.8 min on the linkage map and analysis of
RT   its sequence features.";
RL   DNA Res. 4:91-113(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND SEQUENCE REVISION.
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-103.
RC   STRAIN=K12;
RX   PubMed=8820648; DOI=10.1046/j.1365-2958.1996.424950.x;
RA   Jordan A., Aragall E., Gibert I., Barbe J.;
RT   "Promoter identification and expression analysis of Salmonella typhimurium
RT   and Escherichia coli nrdEF operons encoding one of two class I
RT   ribonucleotide reductases present in both bacteria.";
RL   Mol. Microbiol. 19:777-790(1996).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 544-566.
RX   PubMed=2158980; DOI=10.1128/jb.172.5.2774-2778.1990;
RA   Kubo K.M., Craig N.L.;
RT   "Bacterial transposon Tn7 utilizes two different classes of target sites.";
RL   J. Bacteriol. 172:2774-2778(1990).
RN   [6]
RP   INDUCTION BY HYDROXYUREA.
RC   STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX   PubMed=20005847; DOI=10.1016/j.molcel.2009.11.024;
RA   Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J.,
RA   Walker G.C.;
RT   "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia
RT   coli.";
RL   Mol. Cell 36:845-860(2009).
CC   -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC       Catalyzes the biosynthesis of deoxyribonucleotides from the
CC       corresponding ribonucleotides. R1E contains the binding sites for both
CC       substrates and allosteric effectors and carries out the actual
CC       reduction of the ribonucleotide.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-
CC         diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-
CC         diphosphate; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC         COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1;
CC   -!- ACTIVITY REGULATION: Under complex allosteric control mediated by
CC       deoxynucleoside triphosphates and ATP binding. The type of nucleotide
CC       bound at the specificity site determines substrate preference. It seems
CC       probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP
CC       reduction and dTTP favors GDP reduction (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Tetramer of two alpha and two beta subunits. {ECO:0000250}.
CC   -!- INDUCTION: Induced 2-fold by hydroxyurea.
CC       {ECO:0000269|PubMed:20005847}.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC       chain family. {ECO:0000305}.
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DR   EMBL; U00096; AAC75722.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAA16539.2; -; Genomic_DNA.
DR   EMBL; X79787; CAA56186.1; -; Genomic_DNA.
DR   EMBL; M31530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; D65047; D65047.
DR   RefSeq; NP_417161.1; NC_000913.3.
DR   RefSeq; WP_000246534.1; NZ_LN832404.1.
DR   AlphaFoldDB; P39452; -.
DR   SMR; P39452; -.
DR   BioGRID; 4259221; 220.
DR   BioGRID; 851487; 1.
DR   ComplexPortal; CPX-5157; Ribonucleoside-diphosphate reductase 2 complex.
DR   IntAct; P39452; 9.
DR   STRING; 511145.b2675; -.
DR   PaxDb; 511145-b2675; -.
DR   EnsemblBacteria; AAC75722; AAC75722; b2675.
DR   GeneID; 947155; -.
DR   KEGG; ecj:JW2650; -.
DR   KEGG; eco:b2675; -.
DR   PATRIC; fig|1411691.4.peg.4066; -.
DR   EchoBASE; EB4158; -.
DR   eggNOG; COG0209; Bacteria.
DR   HOGENOM; CLU_000404_4_1_6; -.
DR   InParanoid; P39452; -.
DR   OMA; TLFMTDK; -.
DR   OrthoDB; 9762933at2; -.
DR   PhylomeDB; P39452; -.
DR   BioCyc; EcoCyc:NRDE-MONOMER; -.
DR   BioCyc; MetaCyc:NRDE-MONOMER; -.
DR   BRENDA; 1.17.4.1; 2026.
DR   PRO; PR:P39452; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IGI:EcoliWiki.
DR   GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR   GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IEA:UniProtKB-EC.
DR   GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; ISS:ComplexPortal.
DR   GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IGI:EcoliWiki.
DR   GO; GO:0006260; P:DNA replication; IEA:InterPro.
DR   GO; GO:0015949; P:nucleobase-containing small molecule interconversion; IGI:EcoliWiki.
DR   GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; ISS:ComplexPortal.
DR   CDD; cd01679; RNR_I; 1.
DR   Gene3D; 1.10.1650.20; -; 1.
DR   Gene3D; 3.20.70.20; -; 1.
DR   InterPro; IPR013346; NrdE_NrdA_C.
DR   InterPro; IPR026459; RNR_1b_NrdE.
DR   InterPro; IPR000788; RNR_lg_C.
DR   InterPro; IPR013509; RNR_lsu_N.
DR   InterPro; IPR013554; RNR_N.
DR   InterPro; IPR008926; RNR_R1-su_N.
DR   InterPro; IPR039718; Rrm1.
DR   NCBIfam; TIGR02506; NrdE_NrdA; 1.
DR   NCBIfam; TIGR04170; RNR_1b_NrdE; 1.
DR   PANTHER; PTHR11573; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE LARGE CHAIN; 1.
DR   PANTHER; PTHR11573:SF6; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE LARGE SUBUNIT; 1.
DR   Pfam; PF02867; Ribonuc_red_lgC; 1.
DR   Pfam; PF00317; Ribonuc_red_lgN; 1.
DR   Pfam; PF08343; RNR_N; 1.
DR   PRINTS; PR01183; RIBORDTASEM1.
DR   SUPFAM; SSF51998; PFL-like glycyl radical enzymes; 1.
DR   SUPFAM; SSF48168; R1 subunit of ribonucleotide reductase, N-terminal domain; 1.
DR   PROSITE; PS00089; RIBORED_LARGE; 1.
PE   2: Evidence at transcript level;
KW   Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW   Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..714
FT                   /note="Ribonucleoside-diphosphate reductase 2 subunit
FT                   alpha"
FT                   /id="PRO_0000187224"
FT   ACT_SITE        386
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        388
FT                   /note="Cysteine radical intermediate"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        390
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         161
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         177..178
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         206
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         386..390
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         588..592
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            178
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            185
FT                   /note="Allosteric effector binding"
FT                   /evidence="ECO:0000250"
FT   SITE            215
FT                   /note="Allosteric effector binding"
FT                   /evidence="ECO:0000250"
FT   SITE            415
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            692
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            693
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            709
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   SITE            712
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   DISULFID        178..415
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        545
FT                   /note="K -> P (in Ref. 5; M31530)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        548
FT                   /note="K -> H (in Ref. 5; M31530)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        551..552
FT                   /note="EL -> AP (in Ref. 5; M31530)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        556
FT                   /note="S -> R (in Ref. 5; M31530)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   714 AA;  80479 MW;  6DAD735BF78C1B77 CRC64;
     MATTTAECLT QETMDYHALN AMLNLYDSAG RIQFDKDRQA VDAFIATHVR PNSVTFSSQQ
     QRLNWLVNEG YYDESVLNRY SRDFVITLFT HAHTSGFRFQ TFLGAWKFYT SYTLKTFDGK
     RYLEDFADRV TMVALTLAQG DETLALQLTD EMLSGRFQPA TPTFLNCGKQ QRGELVSCFL
     LRIEDNMESI GRAVNSALQL SKRGGGVAFL LSNLREAGAP IKRIENQSSG VIPVMKMLED
     AFSYANQLGA RQGAGAVYLH AHHPDILRFL DTKRENADEK IRIKTLSLGV VIPDITFHLA
     KENAQMALFS PYDVERVYGK PFADVAISQH YDELVADERI RKKYLNARDF FQRLAEIQFE
     SGYPYIMYED TVNRANPIAG RINMSNLCSE ILQVNSASEY DENLDYTRTG HDISCNLGSL
     NIAHTMDSPD FARTVETAVR GLTAVSDMSH IRSVPSIEAG NAASHAIGLG QMNLHGYLAR
     EGIAYGSPEA LDFTNLYFYA ITWHALRTSM LLARERGETF AGFKQSRYAS GEYFSQYLQG
     NWQPKTAKVG ELFTRSGITL PTREMWAQLR DDVMRYGIYN QNLQAVPPTG SISYINHATS
     SIHPIVAKVE IRKEGKTGRV YYPAPFMTNE NLALYQDAYE IGAEKIIDTY AEATRHVDQG
     LSLTLFFPDT ATTRDINKAQ IYAWRKGIKT LYYIRLRQMA LEGTEIEGCV SCAL
//