RIR1_TRYBB
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 03-AUG-2022, entry version 97.
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 -!- PATHWAY: Genetic information processing; DNA replication.
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 PRIDE; O15909; -.
DR UniPathway; UPA00326; -.
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 InterPro; IPR005144; ATP-cone_dom.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR008926; RNR_R1-su_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 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; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 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
