ID RIR1_BUCAP Reviewed; 763 AA. AC Q8K9W3; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 130. DE RecName: Full=Ribonucleoside-diphosphate reductase subunit alpha; DE EC=1.17.4.1; DE AltName: Full=Ribonucleotide reductase; GN Name=nrdA; OrderedLocusNames=BUsg_173; OS Buchnera aphidicola subsp. Schizaphis graminum (strain Sg). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Erwiniaceae; Buchnera. OX NCBI_TaxID=198804; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Sg; RX PubMed=12089438; DOI=10.1126/science.1071278; RA Tamas I., Klasson L., Canbaeck B., Naeslund A.K., Eriksson A.-S., RA Wernegreen J.J., Sandstroem J.P., Moran N.A., Andersson S.G.E.; RT "50 million years of genomic stasis in endosymbiotic bacteria."; RL Science 296:2376-2379(2002). 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=[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 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; AE013218; AAM67739.1; -; Genomic_DNA. DR RefSeq; WP_011053706.1; NC_004061.1. DR AlphaFoldDB; Q8K9W3; -. DR SMR; Q8K9W3; -. DR STRING; 198804.BUsg_173; -. DR KEGG; bas:BUsg_173; -. DR eggNOG; COG0209; Bacteria. DR HOGENOM; CLU_000404_3_0_6; -. DR Proteomes; UP000000416; Chromosome. 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:0009263; P:deoxyribonucleotide biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0006260; P:DNA replication; IEA:InterPro. 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 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. FT CHAIN 1..763 FT /note="Ribonucleoside-diphosphate reductase subunit alpha" FT /id="PRO_0000187207" 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 756 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000250" FT SITE 761 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000250" FT DISULFID 225..462 FT /note="Redox-active" FT /evidence="ECO:0000250" SQ SEQUENCE 763 AA; 87471 MW; BDE02289A8CF8D3D CRC64; MKNSLFVTKR NGKKEKINLD KIHKVLNWAA KGLENISVSQ VELRSRIQFY NNISTVNIHE TIIKAAADLI SENTPDYQYM AARLAIFHLR KKAYGQFEPP NLYYHVKKMV QLGKYDEKLL QNYSFEEYVE MNSFVDHRRD MNFSYAAVKQ LEAKYLLQNR VTGQIYESAQ FLYILISACL FSKYEKKVRM NYIQRFYNAI STFKISLPTP IMSGVRTPTR QFSSCVLIEC ADNLNSINAT TSAIVKYVSQ RAGIGINAGQ IRALGSPIRN GEAFHTGCIP FYKHFQSAVK SCSQGGVRGG AATVFYPIWH LEIESLLVLK NNRGIEENRV RHLDYAVQIN KLMYQRMLLG QKITLFSPSD VPKLYEFFFS DQKKFKEIYI KYEKNRNIRK KSINAIDLFC LIMRERASTG RIYIQHVDHC NSHSAFNSKL ATIRQSNLCL EITLPTKPLN NIDDKNGEIA LCTLSALNLG LINDLHDLKE LSTLSVRALD EILEYQNYPV VCAKKSAISR RSLGIGVINF AYYLAKNKVR YSDGSAKNLT HKTFEAIQYY LLKASCELAK EKGSCSLFNQ TNYYLGKFPI DTYKKDIDSI CNEPLHLNWN LLRKKIKKYG LRNSTLSALM PSETSSQISN ATNGIEPPRG FISIKSSKDG MLRQVVPEYK KLKSEYELLW EIPNNIGYLE LVAIMQKFVD QSISANTNYD PKRFLNEKIP MKQLIYDLLV AYKLGIKTLY YQNTRDGAED NQNLNKSIEN IKEDNCTSGS CTI //