RIR1_SALTY
ID RIR1_SALTY Reviewed; 761 AA.
AC P37426;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Ribonucleoside-diphosphate reductase 1 subunit alpha;
DE EC=1.17.4.1;
DE AltName: Full=Protein B1;
DE AltName: Full=Ribonucleoside-diphosphate reductase 1 R1 subunit;
DE AltName: Full=Ribonucleotide reductase 1;
GN Name=nrdA; OrderedLocusNames=STM2277;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LT2;
RX PubMed=8195103; DOI=10.1128/jb.176.11.3420-3427.1994;
RA Jordan A., Gibert I., Barbe J.;
RT "Cloning and sequencing of the genes from Salmonella typhimurium encoding a
RT new bacterial ribonucleotide reductase.";
RL J. Bacteriol. 176:3420-3427(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides. R1 contains the binding sites for both
CC substrates and allosteric effectors and carries out the actual
CC reduction of the ribonucleotide.
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 alpha 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: Tetramer of two alpha (R1) and two beta (R2) subunits. The B1
CC protein is a dimer of alpha subunits. A radical transfer pathway occurs
CC between 'Tyr-122' of R2 and R1.
CC -!- MISCELLANEOUS: S.typhimurium produces two separate class I enzymes.
CC This one is the functional enzyme during growth.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; X72948; CAA51452.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL21178.1; -; Genomic_DNA.
DR PIR; S32629; S32629.
DR RefSeq; NP_461219.1; NC_003197.2.
DR RefSeq; WP_001076487.1; NC_003197.2.
DR AlphaFoldDB; P37426; -.
DR SMR; P37426; -.
DR STRING; 99287.STM2277; -.
DR PaxDb; P37426; -.
DR PRIDE; P37426; -.
DR EnsemblBacteria; AAL21178; AAL21178; STM2277.
DR GeneID; 1253799; -.
DR KEGG; stm:STM2277; -.
DR PATRIC; fig|99287.12.peg.2410; -.
DR HOGENOM; CLU_000404_3_0_6; -.
DR OMA; RGSIQNI; -.
DR PhylomeDB; P37426; -.
DR BioCyc; SENT99287:STM2277-MON; -.
DR UniPathway; UPA00326; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IBA:GO_Central.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IBA:GO_Central.
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; Reference proteome.
FT CHAIN 1..761
FT /note="Ribonucleoside-diphosphate reductase 1 subunit
FT alpha"
FT /id="PRO_0000187213"
FT DOMAIN 5..95
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
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 9
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 15..21
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 209
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 232..234
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 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:P00452"
FT BINDING 269
FT /ligand="dTTP"
FT /ligand_id="ChEBI:CHEBI:37568"
FT /ligand_note="allosteric effector that controls substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 437
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 441
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT BINDING 623..625
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P00452"
FT SITE 225
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 462
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 730
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 731
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 754
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 759
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 225..462
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 761 AA; 85736 MW; 0B3322D847CC58F9 CRC64;
MNQSLLVTKR DGRTERINLD KIHRVLDWAA EGLNNVSVSQ VELRSHIQFY DGIKTSDIHE
TIIKAAADLI SRDAPDYQYL AARLAIFHLR KKAFGQFEPP ALYHHVVKMV ELGKYDNHLL
EDYTEEEFKQ MDSFIVHDRD MTFSYAAVKQ LEGKYLVQNR VTGEIYESAQ FLYILVAACL
FSNYPRETRL DYVKRFYDAV STFKISLPTP IMSGVRTPTR QFSSCVLIEC GDSLDSINAT
SSAIVKYVSQ RAGIGINAGR IRALGSPIRG GEAFHTGCIP FYKHFQTAVK SCSQGGVRGG
AATLFYPMWH LEVESLLVLK NNRGVEGNRV RHMDYGVQIN KLMYTRLLKG GDITLFSPSD
VPGLYDAFFA DQDEFERLYV KYEHDDSIRK QRVKAVELFS LMMQERASTG RIYIQNVDHC
NTHSPFDPVV APVRQSNLCL EIALPTKPLN DVNDENGEIA LCTLSAFNLG AIKTLDELEE
LAILAVRALD ALLDYQDYPI PAAKRGAMGR RTLGIGVINF AYWLAKNGKR YSDGSANNLT
HKTFEAIQYY LLKASNELAK EQGACPWFNE TTYAKGILPI DTYKKDLDAI VNEPLHYDWE
QLRESIKTHG LRNSTLSALM PSETSSQISN ATNGIEPPRG YVSIKASKDG ILRQVVPDYE
HLKDAYELLW EMPNNDGYLQ LVGIMQKFID QSISANTNYD PSRFPSGKVP MQQLLKDLLT
AYKFGVKTLY YQNTRDGAED AQDDLAPSIQ DDGCESGACK I
