O53767 (NRDZ_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonucleoside-diphosphate reductase NrdZ
EC=1.17.4.1

Gene names

Name:	nrdZ
Ordered Locus Names:	Rv0570, MT0596

Organism

Mycobacterium tuberculosis [Reference proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Actinobacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	692 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides By similarity.
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin.
Pathway	Genetic information processing; DNA replication.
Induction	A member of the dormancy regulon. Induced in response to reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and carbon monoxide (CO). It is hoped that this regulon will give insight into the latent, or dormant phase of infection. Ref.4 Ref.6 Ref.7
Disruption phenotype	No visible phenotype, even under low-oxygen growth conditions, nor in aerosol-infected B6D2/F1 mice. Ref.3
Miscellaneous	Was identified as a high-confidence drug target.
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family. Contains 1 ATP-cone domain.
Sequence caution	The sequence AAK44819.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	DNA replication
Ligand	ATP-binding Nucleotide-binding
Molecular function	Oxidoreductase
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cell wall Inferred from direct assay PubMed 20825248. Source: MTBBASE cytosol Inferred from direct assay PubMed 15525680. Source: MTBBASE plasma membrane Inferred from direct assay PubMed 14532352PubMed 15525680. Source: MTBBASE ribonucleoside-diphosphate reductase complex Inferred from electronic annotation. Source: InterPro
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cobalamin binding Inferred from electronic annotation. Source: InterPro ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 692	692	Ribonucleoside-diphosphate reductase NrdZ		PRO_0000392684
Regions
	Domain	7 – 95	89	ATP-cone
	Region	192 – 193	2	Substrate binding By similarity
	Region	375 – 379	5	Substrate binding By similarity
	Region	520 – 524	5	Substrate binding By similarity
Sites
	Active site	375	1	Proton acceptor By similarity
	Active site	377	1	Cysteine radical intermediate By similarity
	Active site	379	1	Proton acceptor By similarity
	Binding site	177	1	Substrate By similarity
	Binding site	221	1	Substrate; via amide nitrogen By similarity
	Site	193	1	Important for hydrogen atom transfer By similarity
	Site	200	1	Allosteric effector binding By similarity
	Site	230	1	Allosteric effector binding By similarity
	Site	388	1	Important for hydrogen atom transfer By similarity
	Site	690	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	193 ↔ 388		Redox-active By similarity
Natural variations
	Natural variant	667	1	Y → S in strain: CDC 1551 / Oshkosh.

Sequences

	Sequence		Length	Mass (Da)
	O53767 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 03545540F946656E	FASTA	692	74,521
	10 20 30 40 50 60 MGVSWPAKVR RRDGTLVPFD IARIEAAVTR AAREVACDDP DMPGTVAKAV ADALGRGIAP 70 80 90 100 110 120 VEDIQDCVEA RLGEAGLDDV ARVYIIYRQR RAELRTAKAL LGVRDELKLS LAAVTVLRER 130 140 150 160 170 180 YLLHDEQGRP AESTGELMDR SARCVAAAED QYEPGSSRRW AERFATLLRN LEFLPNSPTL 190 200 210 220 230 240 MNSGTDLGLL AGCFVLPIED SLQSIFATLG QAAELQRAGG GTGYAFSHLR PAGDRVASTG 250 260 270 280 290 300 GTASGPVSFL RLYDSAAGVV SMGGRRRGAC MAVLDVSHPD ICDFVTAKAE SPSELPHFNL 310 320 330 340 350 360 SVGVTDAFLR AVERNGLHRL VNPRTGKIVA RMPAAELFDA ICKAAHAGGD PGLVFLDTIN 370 380 390 400 410 420 RANPVPGRGR IEATNPCGEV PLLPYESCNL GSINLARMLA DGRVDWDRLE EVAGVAVRFL 430 440 450 460 470 480 DDVIDVSRYP FPELGEAARA TRKIGLGVMG LAELLAALGI PYDSEEAVRL ATRLMRRIQQ 490 500 510 520 530 540 AAHTASRRLA EERGAFPAFT DSRFARSGPR RNAQVTSVAP TGTISLIAGT TAGIEPMFAI 550 560 570 580 590 600 AFTRAIVGRH LLEVNPCFDR LARDRGFYRD ELIAEIAQRG GVRGYPRLPA EVRAAFPTAA 610 620 630 640 650 660 EIAPQWHLRM QAAVQRHVEA AVSKTVNLPA TATVDDVRAI YVAAWKAKVK GITVYRYGSR 670 680 690 EGQVLSYAAP KPLLAQADTE FSGGCAGRSC EF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Ribonucleotide reduction in Mycobacterium tuberculosis: function and expression of genes encoding class Ib and class II ribonucleotide reductases." Dawes S.S., Warner D.F., Tsenova L., Timm J., McKinney J.D., Kaplan G., Rubin H., Mizrahi V. Infect. Immun. 71:6124-6131(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE. Strain: ATCC 25618 / H37Rv.
[4]	"Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program." Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M., Sherman D.R., Schoolnik G.K. J. Exp. Med. 198:705-713(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, DORMANCY REGULON. Strain: 1254, ATCC 25618 / H37Rv and CDC 1551 / Oshkosh.
[5]	"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis." Raman K., Yeturu K., Chandra N. BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[6]	"Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection." Shiloh M.U., Manzanillo P., Cox J.S. Cell Host Microbe 3:323-330(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY CARBON MONOXIDE (CO). Strain: ATCC 35801 / TMC 107 / Erdman.
[7]	"Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon." Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I., Agarwal A., Steyn A.J. J. Biol. Chem. 283:18032-18039(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY CARBON MONOXIDE (CO), DORMANCY REGULON. Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842573 Genomic DNA. Translation: CAA17441.1. AE000516 Genomic DNA. Translation: AAK44819.1. Different initiation. AL123456 Genomic DNA. Translation: CCP43308.1.
PIR	A70933.
RefSeq	NP_215084.1. NC_000962.3. NP_335005.1. NC_002755.2. YP_006513903.1. NC_018143.1.
3D structure databases
ProteinModelPortal	O53767.
SMR	O53767. Positions 61-659.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv0570.
Proteomic databases
PRIDE	O53767.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAK44819; AAK44819; MT0596.
GeneID	13318445. 887666. 924988.
KEGG	mtc:MT0596. mtu:Rv0570. mtv:RVBD_0570.
PATRIC	18123012. VBIMycTub22151_0639.
Organism-specific databases
TubercuList	Rv0570.
Phylogenomic databases
eggNOG	COG0209.
HOGENOM	HOG000229277.
KO	K00525.
OMA	QMATFDI.
ProtClustDB	CLSK790600.
Enzyme and pathway databases
UniPathway	UPA00326.
Family and domain databases
InterPro	IPR005144. ATP-cone. IPR000788. RNR_lg_C. IPR013509. RNR_lsu_N. IPR013344. RNR_NrdJ/NrdZ. IPR008926. RNR_R1-su_N. [Graphical view]
Pfam	PF03477. ATP-cone. 1 hit. PF02867. Ribonuc_red_lgC. 2 hits. PF00317. Ribonuc_red_lgN. 1 hit. [Graphical view]
PRINTS	PR01183. RIBORDTASEM1.
SUPFAM	SSF48168. Ribonucleo_red_N. 1 hit.
TIGRFAMs	TIGR02504. NrdJ_Z. 1 hit.
PROSITE	PS51161. ATP_CONE. 1 hit. PS00089. RIBORED_LARGE. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

NRDZ_MYCTU

Accession

Primary (citable) accession number: O53767
Secondary accession number(s): L0T6W6, Q8VKI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 23, 2010
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program