ID RIR1_HAEIN Reviewed; 756 AA. AC P43754; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 142. DE RecName: Full=Ribonucleoside-diphosphate reductase subunit alpha; DE EC=1.17.4.1; DE AltName: Full=Ribonucleotide reductase; GN Name=nrdA; OrderedLocusNames=HI_1659; OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Pasteurellales; OC Pasteurellaceae; Haemophilus. OX NCBI_TaxID=71421; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd; RX PubMed=7542800; DOI=10.1126/science.7542800; RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F., RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M., RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D., RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F., RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R., RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D., RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A., RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.; RT "Whole-genome random sequencing and assembly of Haemophilus influenzae RT Rd."; RL Science 269:496-512(1995). 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 -!- SEQUENCE CAUTION: CC Sequence=AAC23305.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; L42023; AAC23305.1; ALT_INIT; Genomic_DNA. DR PIR; B64135; B64135. DR RefSeq; NP_439801.2; NC_000907.1. DR AlphaFoldDB; P43754; -. DR SMR; P43754; -. DR STRING; 71421.HI_1659; -. DR EnsemblBacteria; AAC23305; AAC23305; HI_1659. DR KEGG; hin:HI_1659; -. DR PATRIC; fig|71421.8.peg.1737; -. DR eggNOG; COG0209; Bacteria. DR HOGENOM; CLU_000404_3_0_6; -. DR OrthoDB; 9762933at2; -. DR PhylomeDB; P43754; -. DR BioCyc; HINF71421:G1GJ1-1676-MONOMER; -. DR Proteomes; UP000000579; Chromosome. DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IBA:GO_Central. DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IBA:GO_Central. DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IBA:GO_Central. 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..756 FT /note="Ribonucleoside-diphosphate reductase subunit alpha" FT /id="PRO_0000187214" 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 749 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000250" FT SITE 754 FT /note="Interacts with thioredoxin/glutaredoxin" FT /evidence="ECO:0000250" FT DISULFID 225..462 FT /note="Redox-active" FT /evidence="ECO:0000250" SQ SEQUENCE 756 AA; 85696 MW; 839D02FA61E185D3 CRC64; MNKSLMVTKR DGTQEQINLD KIHRVITWAA EGLDNVSVSQ VELRSHIQFY EGIRTSDIHE TIIKAAADLI SKDSPDYQYL AARLAIFHLR KKAYGHFDPP RLYDHVKKLV RMEKYDQALL DDYTREEWDT MDGFIDHWRD MTFSYAAVKQ LEGKYLVQNR VTGEIYESAQ FLYLLVSASL FSKYPKETRL DYVKRFYDAT STFKISLPTP IMAGVRTPTR QFSSCVLIEC DDSLDSINAT ASAIVKYVSQ RAGIGINAGA IRALGSEIRG GEAFHTGCIP FYKYFQTAVK SCSQGGVRGG AATLYYPIWH LEAENLLVLK NNRGVEDNRV RHMDYGVQLN KLMYQRLIKG SEITLFSPSD VPGLYEAFFA DQDKFEELYV KYEQDPTIRK RTVKAVEIFS LLMQERASTG RIYIQNVDHC NTHSPFDPQV APVRQSNLCL EIALPTKPLQ HINDENGEIA LCTLSAFNLG KIENLDELEE LADLAVRSLD ALLDYQDYPV VAAKRSSLAR RSLGIGVINY AYYLAKNGVR YSDGSANDLT HRTFEAIQYY LLKASMNLAK EQGACEYFNE TTYAKGILPI DTYKKDLDSL TQEPLHYDWE SLRKDIQEFG LRNSTLTALM PSETSSQISN ATNGIEPPRG HVSIKASKDG ILKQVVPEYE NLMDNYELLW DIPSNDGYLH LVGIMQKFVD QAISANTNYD PKRFEDGKVP MKVLLKDLLT AYKYGLKTLY YQNTRDGAED VQEDLDDGCA GGACKI //