ID   RIR1_TRYBB              Reviewed;         838 AA.
AC   O15909;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   24-JAN-2024, entry version 103.
DE   RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE            EC=1.17.4.1 {ECO:0000269|PubMed:9192674};
DE   AltName: Full=Ribonucleotide reductase R1 subunit {ECO:0000303|PubMed:9192674};
GN   Name=RNR1;
OS   Trypanosoma brucei brucei.
OC   Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC   Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX   NCBI_TaxID=5702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP   REGULATION.
RC   STRAIN=427;
RX   PubMed=9192674; DOI=10.1073/pnas.94.13.6959;
RA   Hofer A., Schmidt P.P., Graslund A., Thelander L.;
RT   "Cloning and characterization of the R1 and R2 subunits of ribonucleotide
RT   reductase from Trypanosoma brucei.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:6959-6964(1997).
CC   -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC       Catalyzes the rate limiting step in the de novo synthesis of
CC       deoxyribonucleotides by directly reducing ribonucleotides to the
CC       corresponding deoxyribonucleotides. {ECO:0000269|PubMed:9192674}.
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:0000269|PubMed:9192674};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23254;
CC         Evidence={ECO:0000269|PubMed:9192674};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[thioredoxin]-disulfide + dCDP + H2O = [thioredoxin]-dithiol +
CC         CDP; Xref=Rhea:RHEA:28038, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC         COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC         ChEBI:CHEBI:58069, ChEBI:CHEBI:58593; EC=1.17.4.1;
CC         Evidence={ECO:0000269|PubMed:9192674};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:28040;
CC         Evidence={ECO:0000269|PubMed:9192674};
CC   -!- ACTIVITY REGULATION: Under complex allosteric control mediated by
CC       deoxynucleoside triphosphates and ATP binding to separate specificity
CC       and activation sites on the large 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.
CC       {ECO:0000269|PubMed:9192674}.
CC   -!- SUBUNIT: Heterodimer of a large and a small subunit.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC       chain family. {ECO:0000305}.
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DR   EMBL; U80910; AAB70704.1; -; mRNA.
DR   AlphaFoldDB; O15909; -.
DR   SMR; O15909; -.
DR   GO; GO:0005654; C:nucleoplasm; IDA:GeneDB.
DR   GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; TAS:GeneDB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:GeneDB.
DR   GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006260; P:DNA replication; ISM:GeneDB.
DR   CDD; cd01679; RNR_I; 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   1: Evidence at protein level;
KW   Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW   Disulfide bond; Nucleotide-binding; Oxidoreductase.
FT   CHAIN           1..838
FT                   /note="Ribonucleoside-diphosphate reductase large subunit"
FT                   /id="PRO_0000187199"
FT   DOMAIN          6..97
FT                   /note="ATP-cone"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT   REGION          780..838
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        780..809
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
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         10..11
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         16..22
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         58
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         62
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         227
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         236..238
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         253
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         266
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         273..274
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         437
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         441
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         626..629
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   SITE            228
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            454
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            759
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            760
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            833
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   SITE            836
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   DISULFID        228..454
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   838 AA;  94619 MW;  19A9B95525BAF69A CRC64;
     MLETVKLVTK RDGSVEPYDE KVVRSRIVNL MSGIDSYYVD VDDLVRVVGE GVREGMSTSM
     LDELLAETAA YCVTKHPDYG LLAGRLAVTA LHKTTTESVL DSFRVLHEHV SQATKRHAPL
     ISEELWDIAN KHSAALQQII NYERDFDFEY FGYKTLERSY LLRVHKGRGV MEVVERPQQM
     FLRVALGIHG EDLERVKETY DYMSQGFFTH ATPTLFNAGT PFPQMSSCFL VAMREDSIDG
     IYDTLKQCAI ISKSAGGIGI HMHNIRAAGS YIAGTNGTSN GLVPMLRVWN NTARYVDQGG
     GKRKGAFAIY LEPWHADIFG FLLLKKNTGK EDQRARDLFY GLWIPDLFME RVESHGTWTL
     MDPNTAPFLS DCYGQEFTDL YERYEREGRG VRTIQAQELW FLILESQVET GVPFMLYKDA
     CNFKSNQKNL GTIKCSNLCT EIVEYTSRDE VAVCNLASIA LPRFVKDGAF DYVALKEVTK
     VVTRNLNRVI DRNHYPVCEA RYSNLRHRPV GIGVQGLADA FALLSLPFAH PEAKKLNRQI
     FETIYIAAVE ASTELAEKDG PYETFKGSPA SEGKLQFDLW DEERRIRGMN EDSVHSHCGL
     WDWDSLKERV VKVGMRNSLL IAPMPTASTS QILGNNECIE PFTSNIYVRR VLSGEFPVVN
     KHLVKELIRL RLWNDDMRRK IIALNGSVSG IKEIPERIRE LYKVVWEIRQ KDLIDMAADR
     GRYIDQSQSL NLFLATPTSS QLTSMHFYSW KKGLKTGMYY LRSQPAADAI KFTLDPKAMK
     ELPKPDKQSK EEVHGSVGRG KRKRVGEKPT ANHSNAGAPN LNGPPDTDGD GGCLNCGS
//