RIR1_PLAF4
ID RIR1_PLAF4 Reviewed; 806 AA.
AC P50648;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 91.
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 Dd2).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=57267;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8265664; DOI=10.1073/pnas.90.24.12020;
RA Chakrabarti D., Schuster S.M., Chakrabarti R.;
RT "Cloning and characterization of subunit genes of ribonucleotide reductase,
RT a cell-cycle-regulated enzyme, from Plasmodium falciparum.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:12020-12024(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}.
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; U01323; AAA50171.1; -; mRNA.
DR AlphaFoldDB; P50648; -.
DR SMR; P50648; -.
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 2: Evidence at transcript level;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..806
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187198"
FT DOMAIN 1..91
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 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 215
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 224..226
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 241
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 254
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 261..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: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 604..607
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT SITE 216
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 737
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 738
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 801
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 804
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 216..442
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 806 AA; 92513 MW; A23B414A687B275F CRC64;
MYVLNRKGEE EDISFDQILK RIQRLSYGLH ELVDPARVTQ GVINGMYSGI KTCELDELAA
QTCAYMATTH PDFSILAARI TTDNLHKNTS DDVAEVAEAL YTYKDVRGRP ASLISKEVYD
FILLHKDRLN KEIDYTRDFN YDYFGFKTLE RSYLLRINNK IIERPQHLLM RVSIGIHIDD
IDKALETYHL MSQKYFTHAT PTLFNSGTPR PQMSSCFLLS MKADSIEGIF ETLKQCALIS
KTAGGIGVAV QDIRGQNSYI RGTNGISNGL VPMLRVFNDT ARYVDQGGGK RKGSFAVYIE
PWHSDIFEFL DLRKNHGKEE LRARDLFYAV WVPDLFMKRV KENKNWTLMC PNECPGLSET
WGEEFEKLYT KYEEENMGKK TVLAQDLWFA ILQSQIETGV PYMLYKDSCN AKSNQKNLGT
IKCSNLCCEI IEYTSPDEVA VCNLASIALC KFVDLEKKEF NFKKLYEITK IITRNLDKII
ERNYYPVKEA KTSNTRHRPI GIGVQGLADT FMLLRYPYES DAAKELNKRI FETMYYAALE
MSVELASIHG PYESYQGSPA SQGILQFDMW NAKVDNKYWD WDELKAKIRK HGLRNSLLLA
PMPTASTSQI LGNNESFEPY TSNIYYRRVL SGEFFVVNPH LLKDLFDRGL WDEDMKQQLI
AHNGSIQYIS EIPDDLKELY KTVWEIKQKN IIDMAADRGI FIDQSQSLNI YIQKPTFAKL
SSMHFYGWEK GLKTGAYYLR TQAATDAIKF TVDTHVAKNA VKLKNADGVQ ITREVSRETI
STESTVTQNV CPLRRNNDEQ CLMCSG
