NRDZ_MYCTU
ID NRDZ_MYCTU Reviewed; 706 AA.
AC P9WH77; L0T6W6; O53767; Q8VKI9;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 2.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Vitamin B12-dependent ribonucleoside-diphosphate reductase;
DE Short=B12-dependent RNR;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase;
GN Name=nrdZ; OrderedLocusNames=Rv0570;
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 DISRUPTION PHENOTYPE.
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 [3]
RP INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, AND DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12953092; DOI=10.1084/jem.20030205;
RA Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M.,
RA Sherman D.R., Schoolnik G.K.;
RT "Inhibition of respiration by nitric oxide induces a Mycobacterium
RT tuberculosis dormancy program.";
RL J. Exp. Med. 198:705-713(2003).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
RP INDUCTION BY CARBON MONOXIDE (CO).
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007;
RA Shiloh M.U., Manzanillo P., Cox J.S.;
RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during
RT macrophage infection.";
RL Cell Host Microbe 3:323-330(2008).
RN [6]
RP INDUCTION BY CARBON MONOXIDE (CO), AND DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18400743; DOI=10.1074/jbc.m802274200;
RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I.,
RA Agarwal A., Steyn A.J.;
RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium
RT tuberculosis dormancy regulon.";
RL J. Biol. Chem. 283:18032-18039(2008).
RN [7]
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).
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 -!- COFACTOR:
CC Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408;
CC Evidence={ECO:0000250};
CC Note=5'-deoxyadenosylcobalamine (coenzyme B12). {ECO:0000250};
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- INDUCTION: A member of the dormancy regulon. Induced in response to
CC reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and
CC carbon monoxide (CO). It is hoped that this regulon will give insight
CC into the latent, or dormant phase of infection.
CC {ECO:0000269|PubMed:12953092, ECO:0000269|PubMed:18400743,
CC ECO:0000269|PubMed:18474359}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype, even under low-oxygen
CC growth conditions, nor in aerosol-infected B6D2/F1 mice.
CC {ECO:0000269|PubMed:14573627}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase class-2
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP43308.1; Type=Erroneous initiation; Note=Truncated N-terminus.;
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DR EMBL; AL123456; CCP43308.1; ALT_INIT; Genomic_DNA.
DR PIR; A70933; A70933.
DR RefSeq; NP_215084.1; NC_000962.3.
DR AlphaFoldDB; P9WH77; -.
DR SMR; P9WH77; -.
DR STRING; 83332.Rv0570; -.
DR PaxDb; P9WH77; -.
DR GeneID; 887666; -.
DR KEGG; mtu:Rv0570; -.
DR TubercuList; Rv0570; -.
DR eggNOG; COG0209; Bacteria.
DR UniPathway; UPA00326; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IBA:GO_Central.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR CDD; cd02888; RNR_II_dimer; 1.
DR InterPro; IPR005144; ATP-cone_dom.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR013344; RNR_NrdJ/NrdZ.
DR InterPro; IPR008926; RNR_R1-su_N.
DR Pfam; PF03477; ATP-cone; 1.
DR Pfam; PF02867; Ribonuc_red_lgC; 2.
DR Pfam; PF00317; Ribonuc_red_lgN; 1.
DR PRINTS; PR01183; RIBORDTASEM1.
DR SUPFAM; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02504; NrdJ_Z; 1.
DR PROSITE; PS51161; ATP_CONE; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cobalamin; Cobalt; Deoxyribonucleotide synthesis;
KW Disulfide bond; DNA synthesis; Nucleotide-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..706
FT /note="Vitamin B12-dependent ribonucleoside-diphosphate
FT reductase"
FT /id="PRO_0000392684"
FT DOMAIN 21..109
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 391
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 393
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 191
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 206..207
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 389..393
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 534..538
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT DISULFID 207..402
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 706 AA; 76106 MW; D5529CF345C9AB3C CRC64;
MPGERRRFAQ ATKSVGVSWP AKVRRRDGTL VPFDIARIEA AVTRAAREVA CDDPDMPGTV
AKAVADALGR GIAPVEDIQD CVEARLGEAG LDDVARVYII YRQRRAELRT AKALLGVRDE
LKLSLAAVTV LRERYLLHDE QGRPAESTGE LMDRSARCVA AAEDQYEPGS SRRWAERFAT
LLRNLEFLPN SPTLMNSGTD LGLLAGCFVL PIEDSLQSIF ATLGQAAELQ RAGGGTGYAF
SHLRPAGDRV ASTGGTASGP VSFLRLYDSA AGVVSMGGRR RGACMAVLDV SHPDICDFVT
AKAESPSELP HFNLSVGVTD AFLRAVERNG LHRLVNPRTG KIVARMPAAE LFDAICKAAH
AGGDPGLVFL DTINRANPVP GRGRIEATNP CGEVPLLPYE SCNLGSINLA RMLADGRVDW
DRLEEVAGVA VRFLDDVIDV SRYPFPELGE AARATRKIGL GVMGLAELLA ALGIPYDSEE
AVRLATRLMR RIQQAAHTAS RRLAEERGAF PAFTDSRFAR SGPRRNAQVT SVAPTGTISL
IAGTTAGIEP MFAIAFTRAI VGRHLLEVNP CFDRLARDRG FYRDELIAEI AQRGGVRGYP
RLPAEVRAAF PTAAEIAPQW HLRMQAAVQR HVEAAVSKTV NLPATATVDD VRAIYVAAWK
AKVKGITVYR YGSREGQVLS YAAPKPLLAQ ADTEFSGGCA GRSCEF
