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 27-MAR-2024, entry version 97. 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 -!- 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 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:InterPro. 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 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 //