ID RIR1_BUCBP Reviewed; 761 AA. AC Q89AS4; DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 02-SEP-2026, entry version 124. DE RecName: Full=Ribonucleoside-diphosphate reductase subunit alpha; DE EC=1.17.4.1; DE AltName: Full=Ribonucleotide reductase; GN Name=nrdA; OrderedLocusNames=bbp_168; OS Buchnera aphidicola subsp. Baizongia pistaciae (strain Bp). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Erwiniaceae; Buchnera. OX NCBI_TaxID=224915; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bp; RX PubMed=12522265; DOI=10.1073/pnas.0235981100; RA van Ham R.C.H.J., Kamerbeek J., Palacios C., Rausell C., Abascal F., RA Bastolla U., Fernandez J.M., Jimenez L., Postigo M., Silva F.J., RA Tamames J., Viguera E., Latorre A., Valencia A., Moran F., Moya A.; RT "Reductive genome evolution in Buchnera aphidicola."; RL Proc. Natl. Acad. Sci. U.S.A. 100:581-586(2003). CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis. CC Catalyzes the biosynthesis of deoxyribonucleotides from the CC corresponding ribonucleotides (By similarity). {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + [thioredoxin]- CC disulfide + H2O = a ribonucleoside 5'-diphosphate + [thioredoxin]- CC dithiol; 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 to separate specificity CC and activation sites on the alpha subunit. The type of nucleotide bound CC 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. Stimulated by ATP and CC inhibited by dATP binding to the activity site (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Tetramer of two alpha and two beta subunits. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large CC chain family. {ECO:0000305}. 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; AE016826; AAO26901.1; -; Genomic_DNA. DR RefSeq; WP_011091302.1; NC_004545.1. DR AlphaFoldDB; Q89AS4; -. DR SMR; Q89AS4; -. DR STRING; 224915.bbp_168; -. DR KEGG; bab:bbp_168; -. DR eggNOG; COG0209; Bacteria. DR HOGENOM; CLU_000404_3_0_6; -. DR OrthoDB; 9762933at2; -. DR Proteomes; UP000000601; Chromosome. DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IEA:TreeGrafter. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IEA:UniProtKB-EC. DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IEA:InterPro. DR FunFam; 1.10.1650.20:FF:000001; Ribonucleoside-diphosphate reductase; 1. DR Gene3D; 1.10.1650.20; -; 1. DR Gene3D; 3.20.70.20; -; 1. DR InterPro; IPR005144; ATP-cone_dom. DR InterPro; IPR013346; NrdE_NrdA_C. DR InterPro; IPR000788; RNR_lg_C. DR InterPro; IPR013509; RNR_lsu_N. DR InterPro; IPR008926; RNR_R1-su_N. DR InterPro; IPR039718; Rrm1. DR NCBIfam; TIGR02506; NrdE_NrdA; 1. DR NCBIfam; NF006578; PRK09103.1; 1. DR PANTHER; PTHR11573; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE LARGE CHAIN; 1. DR PANTHER; PTHR11573:SF6; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE LARGE SUBUNIT; 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; SSF51998; PFL-like glycyl radical enzymes; 1. DR SUPFAM; SSF48168; R1 subunit of ribonucleotide reductase, N-terminal domain; 1. DR PROSITE; PS51161; ATP_CONE; 1. DR PROSITE; PS00089; RIBORED_LARGE; 1. PE 3: Inferred from homology; KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis; KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome. FT CHAIN 1..761 FT /note="Ribonucleoside-diphosphate reductase subunit alpha" FT /id="PRO_0000187208" FT DOMAIN 5..95 FT /note="ATP-cone" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492" FT ACT_SITE 437 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT ACT_SITE 439 FT /note="Cysteine radical intermediate" FT /evidence="ECO:0000250" FT ACT_SITE 441 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 9 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 15..21 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 55 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 91 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 209 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 232..234 FT /ligand="dTTP" FT /ligand_id="ChEBI:CHEBI:37568" FT /ligand_note="allosteric effector that controls substrate FT specificity" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 262 FT /ligand="dTTP" FT /ligand_id="ChEBI:CHEBI:37568" FT /ligand_note="allosteric effector that controls substrate FT specificity" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 269 FT /ligand="dTTP" FT /ligand_id="ChEBI:CHEBI:37568" FT /ligand_note="allosteric effector that controls substrate FT specificity" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 437 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 441 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000250|UniProtKB:P00452" FT BINDING 623..625 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0000250|UniProtKB:P00452" FT SITE 225 FT /note="Important for hydrogen atom transfer" FT /evidence="ECO:0000250" FT SITE 462 FT /note="Important for hydrogen atom transfer" FT /evidence="ECO:0000250" FT SITE 730 FT /note="Important for electron transfer" FT /evidence="ECO:0000250" FT SITE 731 FT /note="Important for electron transfer" FT /evidence="ECO:0000250" FT SITE 754 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000250" FT SITE 759 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000250" FT DISULFID 225..462 FT /note="Redox-active" FT /evidence="ECO:0000250" SQ SEQUENCE 761 AA; 87124 MW; 7FB14E136283BDCF CRC64; MNQMLFVTKR NGKIELINLD KIHRVLNWAA KGLENISISQ VALKSRIQFY NNIKTTIIHE TIIKAAADLI SENSPDYQYM AARLTIFHLR KKAFGQFNPP NLYDHVKNMI KLEKYDQHLL NDYPKQDFLI MNSFIKHRRD MNFSYAAVKQ LEGKYLIQNR VTKKIYESAQ FLYILISACL FSKYPNETRM KYIKNFYDAI STFKISLPTP IMAGLRTPTR QFSSCVLIES EDNLNSINAT TSAIVKYVSQ RAGIGINAGR IRALGSPIRN GDTLHTGCIP FYKHFQSAVK SCSQGGVRGG AATIFYPIWH FEIESLLVLK NNRGIEENRV RHMDYSVQLN KLMYQRLILG EHITLFSPSD VPNLYDSFFN NQEKFERLYI KYENDKTIRK KKVKASYLFS LMMQERTSTG RIYIQNVDHC NSHSAFNPKI APIRQSNLCL EITLPTKALQ DVHDKNGEIS LCTLSAINLG SLNNLNDLSK LSNLIVRALD SVLDYQEYPI LSAKKSALSR RTLGIGVINF AYYLAKNGVR YSDGSANNLT HRTFEAIQYH LLNASCVLAQ EKGACHWFSH TNYYKGILPI DTYKKNVDEI CNEPLHLDWE LLRKKIKKYG LRNSTLSALM PSETSSQISN ATNGIEPPRG LISIKASKDG MLRQVVPEYK RLKNNYELLW NIPNNTGYLQ LASIMQKFVD QSISANTNYD PKLFPNNKIP MQQLILDLLT AYKLGLKTLY YQNTRDGASD HQTEDIQFSK NENCNHGACK I //