ID RIR1_VZVD Reviewed; 775 AA. AC P09248; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 24-JAN-2024, entry version 106. DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit {ECO:0000255|HAMAP-Rule:MF_04026}; DE Short=R1 {ECO:0000255|HAMAP-Rule:MF_04026}; DE EC=1.17.4.1 {ECO:0000255|HAMAP-Rule:MF_04026}; DE AltName: Full=Ribonucleotide reductase large subunit {ECO:0000255|HAMAP-Rule:MF_04026}; GN Name=RIR1 {ECO:0000255|HAMAP-Rule:MF_04026}; OrderedLocusNames=ORF19; OS Varicella-zoster virus (strain Dumas) (HHV-3) (Human herpesvirus 3). OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes; OC Herpesvirales; Orthoherpesviridae; Alphaherpesvirinae; Varicellovirus; OC Varicellovirus humanalpha3; Human herpesvirus 3. OX NCBI_TaxID=10338; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=3018124; DOI=10.1099/0022-1317-67-9-1759; RA Davison A.J., Scott J.E.; RT "The complete DNA sequence of varicella-zoster virus."; RL J. Gen. Virol. 67:1759-1816(1986). RN [2] RP REVIEW. RX PubMed=18990579; DOI=10.1016/j.tibs.2008.09.008; RA Lembo D., Brune W.; RT "Tinkering with a viral ribonucleotide reductase."; RL Trends Biochem. Sci. 34:25-32(2009). CC -!- FUNCTION: Ribonucleoside-diphosphate reductase holoenzyme provides the CC precursors necessary for viral DNA synthesis. Allows virus growth in CC non-dividing cells, as well as reactivation from latency in infected CC hosts. Catalyzes the biosynthesis of deoxyribonucleotides from the CC corresponding ribonucleotides. {ECO:0000255|HAMAP-Rule:MF_04026}. 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 Evidence={ECO:0000255|HAMAP-Rule:MF_04026}; 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. CC {ECO:0000255|HAMAP-Rule:MF_04026}. CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large CC chain family. {ECO:0000255|HAMAP-Rule:MF_04026}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X04370; CAA27902.1; -; Genomic_DNA. DR PIR; A27343; WMBE19. DR SMR; P09248; -. DR Proteomes; UP000002602; Genome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule. DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IEA:UniProtKB-UniRule. DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniRule. DR GO; GO:0019046; P:release from viral latency; IEA:UniProtKB-KW. DR Gene3D; 3.20.70.20; -; 1. DR HAMAP; MF_04026; HSV_RIR1; 1. DR InterPro; IPR034717; HSV_RIR1. DR InterPro; IPR013346; NrdE_NrdA_C. DR InterPro; IPR000788; RNR_lg_C. DR InterPro; IPR013509; RNR_lsu_N. DR InterPro; IPR039718; Rrm1. DR NCBIfam; TIGR02506; NrdE_NrdA; 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 PRINTS; PR01183; RIBORDTASEM1. DR SUPFAM; SSF51998; PFL-like glycyl radical enzymes; 1. DR PROSITE; PS00089; RIBORED_LARGE; 1. PE 3: Inferred from homology; KW ATP-binding; Disulfide bond; DNA replication; Early protein; KW Nucleotide-binding; Oxidoreductase; Reference proteome; Viral latency; KW Viral reactivation from latency. FT CHAIN 1..775 FT /note="Ribonucleoside-diphosphate reductase large subunit" FT /id="PRO_0000187245" FT ACT_SITE 427 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT ACT_SITE 429 FT /note="Cysteine radical intermediate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT ACT_SITE 431 FT /note="Proton acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT BINDING 200 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT BINDING 215..216 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT BINDING 246 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT BINDING 427..431 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT BINDING 606..610 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT SITE 216 FT /note="Important for hydrogen atom transfer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT SITE 444 FT /note="Important for hydrogen atom transfer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT SITE 750 FT /note="Important for electron transfer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT SITE 751 FT /note="Important for electron transfer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT SITE 770 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT SITE 773 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" FT DISULFID 216..444 FT /note="Redox-active" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026" SQ SEQUENCE 775 AA; 86828 MW; 187695A65EB91B9D CRC64; MEFKRIFNTV HDIINRLCQH GYKEYIIPPE STTPVELMEY ISTIVSKLKA VTRQDERVYR CCGELIHCRI NLRSVSMETW LTSPILCLTP RVRQAIEGRR DEIRRAILEP FLKDQYPALA TLGLQSALKY EDFYLTKLEE GKLESLCQFF LRLAATVTTE IVNLPKIATL IPGINDGYTW TDVCRVFFTA LACQKIVPAT PVMMFLGRET GATASCYLMD PESITVGRAV RAITGDVGTV LQSRGGVGIS LQSLNLIPTE NQTKGLLAVL KLLDCMVMAI NSDCERPTGV CVYIEPWHVD LQTVLATRGM LVRDEIFRCD NIFCCLWTPD LFFERYLSYL KGASNVQWTL FDNRADILRT LHGEAFTSTY LRLEREGLGV SSVPIQDIAF TIIRSAAVTG SPFLMFKDAC NRNYHMNTQG NAITGSNLCT EIVQKADAHQ HGVCNLASIN LTTCLSKGPV SFNLNDLQLT ARTTVIFLNG VLAAGNFPCK KSCKGVKNNR SLGIGIQGLH TTCLRLGFDL TSQPARRLNV QIAELMLYET MKTSMEMCKI GGLAPFKGFT ESKYAKGWLH QDGFSTISYL DLPWCTLRDD ICAYGLYNSQ FLALMPTVSS AQVTECSEGF SPIYNNMFSK VTTSGELLRP NLDLMDELRD MYSCEEKRLE VINILEKNQW SVIRSFGCLS NSHPLLKYKT AFEYEQEDLV DMCAERAPFI DQSQSMTLFI EERPDGTIPA SKIMNLLIRA YKAGLKTGMY YCKIRKATNS GLFAGGELTC TSCAL //