P0A5W8 (RIR1_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ribonucleoside-diphosphate reductase subunit alpha
EC=1.17.4.1

Alternative name(s):
Ribonucleotide reductase R1 subunit

Gene names

Name:	nrdE
Ordered Locus Names:	Rv3051c, MT3137
ORF Names:	MTV012.66c

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	725 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. When coexpressed in E.coli with nrdF2 the 2 proteins complement a temperature-sensitive E.coli mutant, however coexpression with nrdF1 does not complement. Ref.4
Catalytic activity	2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin. Ref.4
Enzyme regulation	Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction By similarity. CDP reduction is stimulated by dATP. Ref.4
Pathway	Genetic information processing; DNA replication.
Subunit structure	Tetramer of two alpha and two beta subunits Probable.
Induction	Initially decreases as oxygen levels drop, then rises again. Ref.4 Ref.5
Sequence similarities	Belongs to the ribonucleoside diphosphate reductase large chain family.
Sequence caution	The sequence CAA16136.1 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	Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from direct assay Ref.3. Source: MTBBASE deoxyribonucleotide biosynthetic process Inferred from direct assay Ref.3. Source: MTBBASE growth Inferred from mutant phenotype PubMed 12657046. Source: MTBBASE
Cellular_component	plasma membrane Inferred from direct assay PubMed 14532352PubMed 15525680. Source: MTBBASE ribonucleoside-diphosphate reductase complex Inferred from direct assay Ref.4. Source: MTBBASE
Molecular_function	ATP binding Inferred from direct assay Ref.4. Source: MTBBASE CDP reductase activity Inferred from direct assay Ref.4. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 725	725	Ribonucleoside-diphosphate reductase subunit alpha		PRO_0000187221
Regions
	Region	188 – 189	2	Substrate binding By similarity
	Region	397 – 401	5	Substrate binding By similarity
	Region	599 – 603	5	Substrate binding By similarity
Sites
	Active site	397	1	Proton acceptor By similarity
	Active site	399	1	Cysteine radical intermediate By similarity
	Active site	401	1	Proton acceptor By similarity
	Binding site	172	1	Substrate By similarity
	Binding site	217	1	Substrate; via amide nitrogen By similarity
	Site	189	1	Important for hydrogen atom transfer By similarity
	Site	196	1	Allosteric effector binding By similarity
	Site	226	1	Allosteric effector binding By similarity
	Site	426	1	Important for hydrogen atom transfer By similarity
	Site	703	1	Important for electron transfer By similarity
	Site	704	1	Important for electron transfer By similarity
	Site	720	1	Interacts with thioredoxin/glutaredoxin By similarity
	Site	723	1	Interacts with thioredoxin/glutaredoxin By similarity
Amino acid modifications
	Disulfide bond	189 ↔ 426		Redox-active By similarity
Experimental info
	Sequence conflict	230 – 231	2	AP → GA in AAA64444. Ref.3
	Sequence conflict	457 – 458	2	SD → RH in AAA64444. Ref.3
	Sequence conflict	622	1	I → V in AAA64444. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P0A5W8 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: 38C315D149331D55	FASTA	725	82,441
	10 20 30 40 50 60 MPPTVIAEPV ASGAHASYSG GPGETDYHAL NAMLNLYDAD GKIQFDKDRE AAHQYFLQHV 70 80 90 100 110 120 NQNTVFFHNQ DEKLDYLIRE NYYEREVLDQ YSRNFVKTLL DRAYAKKFRF PTFLGAFKYY 130 140 150 160 170 180 TSYTLKTFDG KRYLERFEDR VVMVALTLAA GDTALAELLV DEIIDGRFQP ATPTFLNSGK 190 200 210 220 230 240 KQRGEPVSCF LLRVEDNMES IGRSINSALQ LSKRGGGVAL LLTNIREHGA PIKNIENQSS 250 260 270 280 290 300 GVIPIMKLLE DAFSYANQLG ARQGAGAVYL HAHHPDIYRF LDTKRENADE KIRIKTLSLG 310 320 330 340 350 360 VVIPDITFEL AKRNDDMYLF SPYDVERVYG VPFADISVTE KYYEMVDDAR IRKTKIKARE 370 380 390 400 410 420 FFQTLAELQF ESGYPYIMFE DTVNRANPID GKITHSNLCS EILQVSTPSL FNEDLSYAKV 430 440 450 460 470 480 GKDISCNLGS LNIAKTMDSP DFAQTIEVAI RALTAVSDQT HIKSVPSIEQ GNNDSHAIGL 490 500 510 520 530 540 GQMNLHGYLA RERIFYGSDE GIDFTNIYFY TVLYHALRAS NRIAIERGTH FKGFERSKYA 550 560 570 580 590 600 SGEFFDKYTD QIWEPKTQKV RQLFADAGIR IPTQDDWRRL KESVQAHGIY NQNLQAVPPT 610 620 630 640 650 660 GSISYINHST SSIHPIVSKV EIRKEGKIGR VYYPAPYMTN DNLEYYEDAY EIGYEKIIDT 670 680 690 700 710 720 YAAATQHVDQ GLSLTLFFKD TATTRDVNKA QIYAWRKGIK TLYYIRLRQM ALEGTEVEGC VSCML

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]	"Isolation of ribonucleotide reductase from Mycobacterium tuberculosis and cloning, expression, and purification of the large subunit." Yang F., Lu G., Rubin H. J. Bacteriol. 176:6738-6743(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3-725. Strain: ATCC 35801 / TMC 107 / Erdman.
[4]	"Characterization of two genes encoding the Mycobacterium tuberculosis ribonucleotide reductase small subunit." Yang F., Curran S.C., Li L.S., Avarbock D., Graf J.D., Chua M.M., Lu G., Salem J., Rubin H. J. Bacteriol. 179:6408-6415(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, FUNCTION IN E.COLI. Strain: ATCC 35801 / TMC 107 / Erdman.
[5]	"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: INDUCTION. Strain: ATCC 25618 / H37Rv.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842581 Genomic DNA. Translation: CAA16136.1. Different initiation. AE000516 Genomic DNA. Translation: AAK47468.1. L34407 Genomic DNA. Translation: AAA64444.1.
PIR	F70861.
RefSeq	NP_217567.1. NC_000962.3. NP_337654.1. NC_002755.2.
3D structure databases
ProteinModelPortal	P0A5W8.
SMR	P0A5W8. Positions 26-710.
ModBase	Search...
Protein-protein interaction databases
STRING	83332.Rv3051c.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	AAK47468; AAK47468; MT3137.
GeneID	888869. 923996.
KEGG	mtc:MT3137. mtu:Rv3051c.
PATRIC	18128658. VBIMycTub22151_3427.
Organism-specific databases
TubercuList	Rv3051c.
Phylogenomic databases
eggNOG	COG0209.
HOGENOM	HOG000246165.
KO	K00525.
OMA	VSRIEIR.
ProtClustDB	PRK08188.
Enzyme and pathway databases
UniPathway	UPA00326.
Family and domain databases
InterPro	IPR013346. NrdE_NrdA. IPR026459. RNR_1b_NrdE. IPR000788. RNR_lg_C. IPR013509. RNR_lsu_N. IPR013554. RNR_N. IPR008926. RNR_R1-su_N. [Graphical view]
Pfam	PF02867. Ribonuc_red_lgC. 1 hit. PF00317. Ribonuc_red_lgN. 1 hit. PF08343. RNR_N. 1 hit. [Graphical view]
PRINTS	PR01183. RIBORDTASEM1.
SUPFAM	SSF48168. Ribonucleo_red_N. 1 hit.
TIGRFAMs	TIGR02506. NrdE_NrdA. 1 hit. TIGR04170. RNR_1b_NrdE. 1 hit.
PROSITE	PS00089. RIBORED_LARGE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

RIR1_MYCTU

Accession

Primary (citable) accession number: P0A5W8
Secondary accession number(s): O53296, P50640

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	May 1, 2013
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program