RIR1_CRYPV
ID RIR1_CRYPV Reviewed; 803 AA.
AC O61065;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Ribonucleoside-diphosphate reductase large chain;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase R1 subunit;
GN Name=RNR1;
OS Cryptosporidium parvum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Cryptosporidiidae; Cryptosporidium.
OX NCBI_TaxID=5807;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=GCH1;
RX PubMed=12391728; DOI=10.1080/10425170290023419;
RA Akiyoshi D.E., Balakrishnan R., Huettinger C., Widmer G., Tzipori S.;
RT "Molecular characterization of ribonucleotide reductase from
RT Cryptosporidium parvum.";
RL DNA Seq. 13:167-172(2002).
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; AF043243; AAC12280.2; -; Genomic_DNA.
DR AlphaFoldDB; O61065; -.
DR SMR; O61065; -.
DR VEuPathDB; CryptoDB:cgd6_1950; -.
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..803
FT /note="Ribonucleoside-diphosphate reductase large chain"
FT /id="PRO_0000187196"
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 798
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 801
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 216..442
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 803 AA; 91123 MW; 9DBE7F2AC337F97F CRC64;
MYVVNRKGEE EPVSFDQILS RITKLSYGLH PLVDPARVTQ AVINGLYSGI KTSELDELAS
QTCAYMAATH NDFSKLAARI STSNLHKNTS SDIGDVASQL YNFKDNQGCP APLISKPVYD
FIMENRERIN SKIDFSKDFE YDYFAFKTLE RSYLLKIDNK VVERPQHLLM RVSCGIHCGD
IEAALETYEL LSQKYFTHAT PTLFNSGTPR PQMSSCFLLR IPEDSINGIF DTLTKCANIS
KTAGGLGVAV SNIRGTGSYI RGTNGRSNGL IPMLRVYNDT ARYIDQGGGK RKGAIAIYLE
PWHVDVVEFI EIRKNHGKEE MRCRDLFPAL WVPDLFMERV EKDQDWTLMC PDECRGLQDV
WGDDFKKLYE EYEKQGRGRK TMKAQKLWFL ILQAQIETGT PFICYKDAAN SKSNQKNLGT
IVSSNLCTEI IEYTSTDEVA VCNLASIGLP KFVDKNNKTF DFDKLKEVTK VITRNLNKLI
DVGYYSLKEC KKSNLRHRPL GIGIQGLADC FMMLRMPYES EGAKKLNKQI FEVIYYAALD
ASCELAEKYG PYETYSGSPA SKGILQFDMW GVTPDSGLCD WDLLKDRISK HGIRNSLLIS
PMPTASTSQI LGNNESFEPF TSNIYHRRVL SGEFFVVNPH LLNDLLELGL WDDRLKQNII
ANNGSIQNIL TIPEDIRELY KTVWEIKQKT VIDMAADRGP YVCQSQSLNI HMENANFAKL
SSMHFYGWKK GLKTGIYYLR TQSATRPIQF TVDQQLLKSE TKEKDSLETN KRQALEPEAQ
KLIACPLRPT NMKDDEECMM CSG
