RIR1_MYCTU
ID RIR1_MYCTU Reviewed; 725 AA.
AC P9WH75; L0TD07; O53296; P0A5W8; P50640;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Ribonucleoside-diphosphate reductase subunit alpha;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase R1 subunit;
GN Name=nrdE; OrderedLocusNames=Rv3051c; ORFNames=MTV012.66c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-725.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=7961427; DOI=10.1128/jb.176.21.6738-6743.1994;
RA Yang F., Lu G., Rubin H.;
RT "Isolation of ribonucleotide reductase from Mycobacterium tuberculosis and
RT cloning, expression, and purification of the large subunit.";
RL J. Bacteriol. 176:6738-6743(1994).
RN [3]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION IN E.COLI.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=9335290; DOI=10.1128/jb.179.20.6408-6415.1997;
RA Yang F., Curran S.C., Li L.S., Avarbock D., Graf J.D., Chua M.M., Lu G.,
RA Salem J., Rubin H.;
RT "Characterization of two genes encoding the Mycobacterium tuberculosis
RT ribonucleotide reductase small subunit.";
RL J. Bacteriol. 179:6408-6415(1997).
RN [4]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14573627; DOI=10.1128/iai.71.11.6124-6131.2003;
RA Dawes S.S., Warner D.F., Tsenova L., Timm J., McKinney J.D., Kaplan G.,
RA Rubin H., Mizrahi V.;
RT "Ribonucleotide reduction in Mycobacterium tuberculosis: function and
RT expression of genes encoding class Ib and class II ribonucleotide
RT reductases.";
RL Infect. Immun. 71:6124-6131(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=32634279; DOI=10.1111/mmi.14571;
RA Zaveri A., Wang R., Botella L., Sharma R., Zhu L., Wallach J.B., Song N.,
RA Jansen R.S., Rhee K.Y., Ehrt S., Schnappinger D.;
RT "Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the
RT DNA-damage response and leads to cell death.";
RL Mol. Microbiol. 114:641-652(2020).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides. When coexpressed in E.coli with nrdF2
CC the 2 proteins complement a temperature-sensitive E.coli mutant,
CC however coexpression with nrdF1 does not complement.
CC {ECO:0000269|PubMed:9335290}.
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 Evidence={ECO:0000269|PubMed:9335290};
CC -!- ACTIVITY REGULATION: Under complex allosteric control mediated by
CC deoxynucleoside triphosphates and ATP binding. The type of nucleotide
CC bound 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 (By similarity). CDP reduction
CC is stimulated by dATP. {ECO:0000250, ECO:0000269|PubMed:9335290}.
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Tetramer of two alpha and two beta subunits (Probable). Co-
CC immunoprecipitates with DarG in the presence and absence of darT
CC (PubMed:32634279). {ECO:0000269|PubMed:32634279, ECO:0000305}.
CC -!- INDUCTION: Initially decreases as oxygen levels drop, then rises again.
CC {ECO:0000269|PubMed:14573627}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP45860.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL123456; CCP45860.1; ALT_INIT; Genomic_DNA.
DR EMBL; L34407; AAA64444.1; -; Genomic_DNA.
DR PIR; F70861; F70861.
DR RefSeq; NP_217567.1; NC_000962.3.
DR RefSeq; WP_003914457.1; NZ_NVQJ01000011.1.
DR AlphaFoldDB; P9WH75; -.
DR SMR; P9WH75; -.
DR STRING; 83332.Rv3051c; -.
DR BindingDB; P9WH75; -.
DR ChEMBL; CHEMBL2346487; -.
DR PaxDb; P9WH75; -.
DR DNASU; 888869; -.
DR GeneID; 888869; -.
DR KEGG; mtu:Rv3051c; -.
DR TubercuList; Rv3051c; -.
DR eggNOG; COG0209; Bacteria.
DR OMA; RGSIQNI; -.
DR BRENDA; 1.17.4.1; 3445.
DR UniPathway; UPA00326; -.
DR PRO; PR:P9WH75; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0051063; F:CDP reductase activity; IDA:MTBBASE.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:MTBBASE.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IDA:MTBBASE.
DR GO; GO:0006260; P:DNA replication; IDA:MTBBASE.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR026459; RNR_1b_NrdE.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR013554; RNR_N.
DR InterPro; IPR008926; RNR_R1-su_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 1.
DR Pfam; PF02867; Ribonuc_red_lgC; 1.
DR Pfam; PF00317; Ribonuc_red_lgN; 1.
DR Pfam; PF08343; RNR_N; 1.
DR PRINTS; PR01183; RIBORDTASEM1.
DR SUPFAM; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 1.
DR TIGRFAMs; TIGR04170; RNR_1b_NrdE; 1.
DR PROSITE; PS00089; RIBORED_LARGE; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..725
FT /note="Ribonucleoside-diphosphate reductase subunit alpha"
FT /id="PRO_0000187221"
FT ACT_SITE 397
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 399
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 401
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 188..189
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 397..401
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 599..603
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 189
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 196
FT /note="Allosteric effector binding"
FT /evidence="ECO:0000250"
FT SITE 226
FT /note="Allosteric effector binding"
FT /evidence="ECO:0000250"
FT SITE 426
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 703
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 704
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 720
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 723
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 189..426
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT CONFLICT 230..231
FT /note="AP -> GA (in Ref. 2; AAA64444)"
FT /evidence="ECO:0000305"
FT CONFLICT 457..458
FT /note="SD -> RH (in Ref. 2; AAA64444)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="I -> V (in Ref. 2; AAA64444)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 725 AA; 82441 MW; 38C315D149331D55 CRC64;
MPPTVIAEPV ASGAHASYSG GPGETDYHAL NAMLNLYDAD GKIQFDKDRE AAHQYFLQHV
NQNTVFFHNQ DEKLDYLIRE NYYEREVLDQ YSRNFVKTLL DRAYAKKFRF PTFLGAFKYY
TSYTLKTFDG KRYLERFEDR VVMVALTLAA GDTALAELLV DEIIDGRFQP ATPTFLNSGK
KQRGEPVSCF LLRVEDNMES IGRSINSALQ LSKRGGGVAL LLTNIREHGA PIKNIENQSS
GVIPIMKLLE DAFSYANQLG ARQGAGAVYL HAHHPDIYRF LDTKRENADE KIRIKTLSLG
VVIPDITFEL AKRNDDMYLF SPYDVERVYG VPFADISVTE KYYEMVDDAR IRKTKIKARE
FFQTLAELQF ESGYPYIMFE DTVNRANPID GKITHSNLCS EILQVSTPSL FNEDLSYAKV
GKDISCNLGS LNIAKTMDSP DFAQTIEVAI RALTAVSDQT HIKSVPSIEQ GNNDSHAIGL
GQMNLHGYLA RERIFYGSDE GIDFTNIYFY TVLYHALRAS NRIAIERGTH FKGFERSKYA
SGEFFDKYTD QIWEPKTQKV RQLFADAGIR IPTQDDWRRL KESVQAHGIY NQNLQAVPPT
GSISYINHST SSIHPIVSKV EIRKEGKIGR VYYPAPYMTN DNLEYYEDAY EIGYEKIIDT
YAAATQHVDQ GLSLTLFFKD TATTRDVNKA QIYAWRKGIK TLYYIRLRQM ALEGTEVEGC
VSCML
