ID RIR1_BUCAI Reviewed; 761 AA. AC P57276; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 1. DT 27-MAR-2024, entry version 127. DE RecName: Full=Ribonucleoside-diphosphate reductase subunit alpha; DE EC=1.17.4.1; DE AltName: Full=Ribonucleotide reductase; GN Name=nrdA; OrderedLocusNames=BU179; OS Buchnera aphidicola subsp. Acyrthosiphon pisum (strain APS) (Acyrthosiphon OS pisum symbiotic bacterium). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Erwiniaceae; Buchnera. OX NCBI_TaxID=107806; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=APS; RX PubMed=10993077; DOI=10.1038/35024074; RA Shigenobu S., Watanabe H., Hattori M., Sakaki Y., Ishikawa H.; RT "Genome sequence of the endocellular bacterial symbiont of aphids Buchnera RT sp. APS."; RL Nature 407:81-86(2000). 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; BA000003; BAB12896.1; -; Genomic_DNA. DR RefSeq; NP_240010.1; NC_002528.1. DR RefSeq; WP_009874136.1; NC_002528.1. DR AlphaFoldDB; P57276; -. DR SMR; P57276; -. DR STRING; 563178.BUAP5A_176; -. DR EnsemblBacteria; BAB12896; BAB12896; BAB12896. DR KEGG; buc:BU179; -. DR PATRIC; fig|107806.10.peg.190; -. DR eggNOG; COG0209; Bacteria. DR HOGENOM; CLU_000404_3_0_6; -. DR Proteomes; UP000001806; 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; Reference proteome. FT CHAIN 1..761 FT /note="Ribonucleoside-diphosphate reductase subunit alpha" FT /id="PRO_0000187206" 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; 87166 MW; 700A2A4AA426AC76 CRC64; MKKNLFVTKR DGRKEKINLD KIHKVLNWAS EGLDDVSVSQ VELCSRIQFY NNITTINIHE TIIKAAADLI SQDTPDYQYM AARLAIFHLR KKAYGQFEPP KLYDHVKKMV DLEKYDENLL KNYSYKEFLQ MNSFIDHWRD MNFSYAAVKQ LEGKYLIQNR VNGKIYESAQ FLYILISACL FSQYPKNVRM NYIHRFYNAI STFKISLPTP IMSGVRTPTR QFSSCVLIEC GDSLNSINAT TSSIVKYVSQ RAGIGVNAGQ IRALGSPIRN GEAFHTGCIP FYKHFQSAVK SCSQGGVRGG AATIFYPIWH LEVESLLVLK NNRGIEENRV RHIDYAIQIN KLMYQRMLSG DQITLFSPSD VPDLYKAFFS DQKKFKKIYL QYEKNKNIRK KTIKALDLFS LMMQERTSTG RIYVQNVDHC NLHSAFNPEL SPIRQSNLCL EITLPTKSLN DVHDTDGEIA LCTLSAFNLG KIKSLDDFKE LSILSVRALD EILDYQNYPV LAAKKSAISR RSLGIGVINF AYYLAKNKVR YSDGSAHNLT HKTFEAMQYY LLEASCELAK EKGACSLFNH TNYYLGKLPI DTYKKYIDDI CNEPLHLDWN LLRSKIKKYG LRNSTLSALM PSETSSQISN ATNGIEPPRG FISIKVSKDG ILRQVVPEYK KLRLQYELLW DIPNNTGYLQ LAGIMQKFID QSISVNTHYD PARFLNNKIP MKQLLYDLLL SYKLGLKTLY YQNTRDGSED DQNITSKSIT EDICESGSCI L //