RIR1_PLAFG
ID RIR1_PLAFG Reviewed; 804 AA.
AC P50647;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase R1 subunit;
GN Name=RNR1;
OS Plasmodium falciparum (isolate FCR-3 / Gambia).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5838;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8415692; DOI=10.1073/pnas.90.20.9280;
RA Rubin H., Salem J.S., Li L.S., Yang F.D., Mama S., Wang Z.M., Fisher A.,
RA Hamann C.S., Cooperman B.S.;
RT "Cloning, sequence determination, and regulation of the ribonucleotide
RT reductase subunits from Plasmodium falciparum: a target for antimalarial
RT therapy.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:9280-9284(1993).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides.
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 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 (By similarity).
CC {ECO:0000250}.
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; AF205580; AAA29755.1; -; Genomic_DNA.
DR PIR; B48687; B48687.
DR AlphaFoldDB; P50647; -.
DR SMR; P50647; -.
DR UniPathway; UPA00326; -.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
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 3: Inferred from homology;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..804
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187197"
FT DOMAIN 1..92
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 425
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 427
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 429
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 5..6
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 11..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 57
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 216
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 225..227
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 242
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 255
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 262..263
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 425
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 429
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 603..606
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT SITE 217
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 442
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 736
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 737
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 799
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 802
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 217..442
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 804 AA; 92403 MW; 8D3C70EA2ED0A6E9 CRC64;
MYVLNRKGEE EDISFDQILK RIQRLSYGLH KLGEYPACVT QGVINGMYSS IKTCELDELA
AQTCAYMATT HPDFSILAAR ITTDNLHKNT SDDVAEVAEA LYTYKDGRGR PASLISKEVY
DFILLHKVRL NKEIDYTTHF NYDYFGFKTL ERSYLLRINN KIIERPQHLL MRVSIGIHID
DIDKALETYH LMSQKYFTHA TPTLFNSGTP RPQMSSCFLL SMKADSIEGI FETLKQCALI
SKTAGGIGVA VQDIRGQNSY IRGTNGISNG LVPMLRVFND TARYVDQGGG KRKGSYAVYI
EPWHSDIFEF LDLRKNHGKE ELRARDLFYA VWVPDLFMKR VKENKNWTLM CPNECPGLSE
TWGEEFEKLY TKYEEENMGK KTVLAQDLWF AILQSQIETG VPIYLYKDSC NAKPIKNLGT
IKCSNLCCEI IEYTSPDEVA VCNLASIALC KFVDLEKKEF NFKKLYEITK IITRNLDKII
ERNYYPVKEA KTSNTRHRPI GIGVQGLADT FMLLRYLYES DAAKELNKRI YETMYYAALE
MSVDWLQSGP YESYQGSPGS QGILQFDMWN AKVDNKYWDW DELKLKIAKT GLRNLLLLAP
MPTASTSQIL GNNESFEPYT SNIYYRRVLS GEFFVVNPHL LKDLFDRGLW DEDMKQQLIA
HNGSIQYISE IPDDLKELYK TVWEIKQKNI IDMAADRGYF IDQSQSLNIY IQKPTFAKLS
SMHFYGWEKG LKTGAYYLRT QAATDAIKFT VDTHVAKNAV KLKNADGVQI TREVSRETIQ
LNQRYSKCVS FKSNNDEQCL MCSG
