RIR1_VACCW
ID RIR1_VACCW Reviewed; 771 AA.
AC P12848; Q76ZU9;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase large subunit;
GN OrderedLocusNames=VACWR073; ORFNames=I4L;
OS Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain
OS WR)).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX NCBI_TaxID=10254;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RX PubMed=2835495; DOI=10.1128/jvi.62.6.1889-1897.1988;
RA Schmitt J.F.C., Stunnenberg H.G.;
RT "Sequence and transcriptional analysis of the vaccinia virus HindIII I
RT fragment.";
RL J. Virol. 62:1889-1897(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3284177; DOI=10.1016/0042-6822(88)90627-7;
RA Tengelsen L.A., Slabaugh M.B., Bibler J.K., Hruby D.E.;
RT "Nucleotide sequence and molecular genetic analysis of the large subunit of
RT ribonucleotide reductase encoded by vaccinia virus.";
RL Virology 164:121-131(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Esposito J.J., Frace A.M., Sammons S.A., Olsen-Rasmussen M., Osborne J.,
RA Wohlhueter R.;
RT "Sequencing of the coding region of Vaccinia-WR to an average 9-fold
RT redundancy and an error rate of 0.16/10kb.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RX PubMed=8349665; DOI=10.1016/s0021-9258(17)46776-7;
RA Slabaugh M.B., Davis R.E., Roseman N.A., Mathews C.K.;
RT "Vaccinia virus ribonucleotide reductase expression and isolation of the
RT recombinant large subunit.";
RL J. Biol. Chem. 268:17803-17810(1993).
CC -!- FUNCTION: Ribonucleoside-diphosphate reductase holoenzyme provides the
CC precursors necessary for viral DNA synthesis. Allows virus growth in
CC non-dividing cells. Catalyzes the biosynthesis of deoxyribonucleotides
CC from the corresponding ribonucleotides (By similarity). {ECO:0000250}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8349665};
CC Note=Maximal ribonucleotide reductase activity requires the presence of
CC Mg(2+) ions. {ECO:0000269|PubMed:8349665};
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, whereas dGTP
CC favors ADP reduction and dTTP favors GDP reduction (By similarity).
CC {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.0 and above. {ECO:0000269|PubMed:8349665};
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterotetramer composed of a homodimer of the large subunit
CC (R1) and a homodimer of the small subunit (R2). Larger multisubunit
CC protein complex are also active, composed of (R1)n(R2)n (By
CC similarity). {ECO:0000250}.
CC -!- INDUCTION: Expressed early in the viral replicative cycle.
CC {ECO:0000269|PubMed:2835495}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; J03399; AAB59806.1; -; Genomic_DNA.
DR EMBL; M20299; AAA48274.1; -; Genomic_DNA.
DR EMBL; AY243312; AAO89352.1; -; Genomic_DNA.
DR PIR; A28611; WZVZH4.
DR RefSeq; YP_232955.1; NC_006998.1.
DR SMR; P12848; -.
DR DIP; DIP-2158N; -.
DR IntAct; P12848; 1.
DR MINT; P12848; -.
DR GeneID; 3707606; -.
DR KEGG; vg:3707606; -.
DR UniPathway; UPA00326; -.
DR Proteomes; UP000000344; Genome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IEA:UniProtKB-EC.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR InterPro; IPR005144; ATP-cone_dom.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR008926; RNR_R1-su_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 1.
DR Pfam; PF03477; ATP-cone; 1.
DR Pfam; PF02867; Ribonuc_red_lgC; 1.
DR Pfam; PF00317; Ribonuc_red_lgN; 1.
DR PRINTS; PR01183; RIBORDTASEM1.
DR SUPFAM; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 1.
DR PROSITE; PS51161; ATP_CONE; 1.
DR PROSITE; PS00089; RIBORED_LARGE; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Early protein; Magnesium; Nucleotide-binding;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..771
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187232"
FT DOMAIN 1..92
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 427
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 429
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 431
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 217..218
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 247
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 427..431
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 602..606
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 218
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 226
FT /note="Allosteric effector binding"
FT /evidence="ECO:0000250"
FT SITE 256
FT /note="Allosteric effector binding"
FT /evidence="ECO:0000250"
FT SITE 444
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 735
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 736
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 766
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 769
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 218..444
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT CONFLICT 447
FT /note="A -> G (in Ref. 2; AAA48274)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="D -> V (in Ref. 2; AAA48274)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="L -> I (in Ref. 2; AAA48274)"
FT /evidence="ECO:0000305"
FT CONFLICT 601..606
FT /note="MPTAST -> LPLHQH (in Ref. 2; AAA48274)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 771 AA; 87738 MW; 6CA07F0C58F6A8F9 CRC64;
MFVIKRNGYK ENVMFDKITS RIRKLCYGLN TDHIDPIKIA MKVIQGIYNG VTTVELDTLA
AEIAATCTTQ HPDYAILAAR IAVSNLHKET KKLFSEVMED LFNYVNPKNG KHSPIISSIT
MDIVNKYKDK LNSVIIYERD FSYNYFGFKT LEKSYLLKIN NKIVERPQHM LMRVAVGIHQ
WDIDSAIETY NLLSEKWFTH ASPTLFNAGT SRHQMSSCFL LNMIDDSIEG IYDTLKRCAL
ISKMAGGIGL SISNIRASGS YISGTNGISN GIIPMLRVYN NTARYIDQGG NKRPGVMAIY
LEPWHSDIMA FLDLKKNTGN EEHRTRDLFI ALWIPDLFMK RVKDDGEWSL MCPDECPGLD
NVWGDEFERL YTLYERERRY KSIIKARVVW KAIIESQIET GTPFILYKDA CNKKSNQQNL
GTIKCSNLCT EIIQYADANE VAVCNLASVA LNMFVIDGRF DFLKLKDVVK VIVRNLNKII
DINYYPIPEA EISNKRHRPI GIGVQGLADA FILLNYPFDS LEAQDLNKKI FETIYYGALE
ASCELAEKEG PYDTYVGSYA SNGILQYDLW NVVPSDLWNW EPLKDKIRTY GLRNSLLVAP
MPTASTAQIL GNNESVEPYT SNIYTRRVLS GEFQVVNPHL LRVLTERKLW NDEIKNRIMA
DGGSIQNTNL PEDIKRVYKT IWEIPQKTII KMAADRGAFI DQSQSMNIHI ADPSYSKLTS
MHFYGWSLGL KTGMYYLRTK PASAPIQFTL DKDKIKPPVV CDSEICTSCS G
