RIR1_HAEIN
ID RIR1_HAEIN Reviewed; 756 AA.
AC P43754;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Ribonucleoside-diphosphate reductase subunit alpha;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase;
GN Name=nrdA; OrderedLocusNames=HI_1659;
OS Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC Pasteurellaceae; Haemophilus.
OX NCBI_TaxID=71421;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX PubMed=7542800; DOI=10.1126/science.7542800;
RA Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F.,
RA Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA Small K.V., Fraser C.M., Smith H.O., Venter J.C.;
RT "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT Rd.";
RL Science 269:496-512(1995).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides (By similarity). {ECO:0000250}.
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 and two beta subunits. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC23305.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L42023; AAC23305.1; ALT_INIT; Genomic_DNA.
DR PIR; B64135; B64135.
DR RefSeq; NP_439801.2; NC_000907.1.
DR RefSeq; WP_005694386.1; NC_000907.1.
DR AlphaFoldDB; P43754; -.
DR SMR; P43754; -.
DR STRING; 71421.HI_1659; -.
DR PRIDE; P43754; -.
DR EnsemblBacteria; AAC23305; AAC23305; HI_1659.
DR KEGG; hin:HI_1659; -.
DR PATRIC; fig|71421.8.peg.1737; -.
DR eggNOG; COG0209; Bacteria.
DR HOGENOM; CLU_000404_3_0_6; -.
DR PhylomeDB; P43754; -.
DR BioCyc; HINF71421:G1GJ1-1676-MON; -.
DR UniPathway; UPA00326; -.
DR Proteomes; UP000000579; 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..756
FT /note="Ribonucleoside-diphosphate reductase subunit alpha"
FT /id="PRO_0000187214"
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 749
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 754
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 225..462
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 756 AA; 85696 MW; 839D02FA61E185D3 CRC64;
MNKSLMVTKR DGTQEQINLD KIHRVITWAA EGLDNVSVSQ VELRSHIQFY EGIRTSDIHE
TIIKAAADLI SKDSPDYQYL AARLAIFHLR KKAYGHFDPP RLYDHVKKLV RMEKYDQALL
DDYTREEWDT MDGFIDHWRD MTFSYAAVKQ LEGKYLVQNR VTGEIYESAQ FLYLLVSASL
FSKYPKETRL DYVKRFYDAT STFKISLPTP IMAGVRTPTR QFSSCVLIEC DDSLDSINAT
ASAIVKYVSQ RAGIGINAGA IRALGSEIRG GEAFHTGCIP FYKYFQTAVK SCSQGGVRGG
AATLYYPIWH LEAENLLVLK NNRGVEDNRV RHMDYGVQLN KLMYQRLIKG SEITLFSPSD
VPGLYEAFFA DQDKFEELYV KYEQDPTIRK RTVKAVEIFS LLMQERASTG RIYIQNVDHC
NTHSPFDPQV APVRQSNLCL EIALPTKPLQ HINDENGEIA LCTLSAFNLG KIENLDELEE
LADLAVRSLD ALLDYQDYPV VAAKRSSLAR RSLGIGVINY AYYLAKNGVR YSDGSANDLT
HRTFEAIQYY LLKASMNLAK EQGACEYFNE TTYAKGILPI DTYKKDLDSL TQEPLHYDWE
SLRKDIQEFG LRNSTLTALM PSETSSQISN ATNGIEPPRG HVSIKASKDG ILKQVVPEYE
NLMDNYELLW DIPSNDGYLH LVGIMQKFVD QAISANTNYD PKRFEDGKVP MKVLLKDLLT
AYKYGLKTLY YQNTRDGAED VQEDLDDGCA GGACKI
