EzCatDB: M00204
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DB codeM00204
CATH domainDomain 11.10.-.-
Domain 21.10.-.-
Domain 33.90.244.10Catalytic domain
Domain 43.90.188.10Catalytic domain
Domain 51.10.620.20 : Ribonucleotide Reductase, subunit ACatalytic domain
E.C.1.17.4.1

CATH domainRelated DB codes (homologues)
1.10.620.20 : Ribonucleotide Reductase, subunit AS00028,M00151,M00205
3.90.188.10M00205
3.90.244.10M00205

Enzyme Name
UniProtKBKEGG

Q08698P17424O69274
Protein nameRibonucleoside-diphosphate reductase 2 subunit alphaRibonucleoside-diphosphate reductase 2 subunit beta
ribonucleoside-diphosphate reductase
ribonucleotide reductase
CDP reductase
ribonucleoside diphosphate reductase
UDP reductase
ADP reductase
nucleoside diphosphate reductase
ribonucleoside 5'-diphosphate reductase
ribonucleotide diphosphate reductase
2'-deoxyribonucleoside-diphosphate:oxidized-thioredoxin2'-oxidoreductase
RR
SynonymsEC 1.17.4.1
Ribonucleotide reductase 2
R1E protein
EC 1.17.4.1
Ribonucleotide reductase 2
R2F protein
Ribonucleotide reductase subunit R2F
RefSeqNP_461733.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
NP_461734.1 (Protein)
NC_003197.1 (DNA/RNA sequence)

PfamPF02867 (Ribonuc_red_lgC)
PF00317 (Ribonuc_red_lgN)
PF08343 (RNR_N)
[Graphical view]
PF00268 (Ribonuc_red_sm)
[Graphical view]
PF00268 (Ribonuc_red_sm)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00230Purine metabolism
MAP00240Pyrimidine metabolism
MAP00480Glutathione metabolism

UniProtKB:Accession NumberQ08698P17424O69274
Entry nameRIR3_SALTYRIR4_SALTYO69274_CORAM
Activity2''-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin.2''-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin.
SubunitTetramer of two alpha and two beta subunits (By similarity).Tetramer of two alpha and two beta subunits (By similarity).
Subcellular location


Cofactor
Binds 2 iron ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00023C07292C03723C04232C07293C00001
CompoundIronGlutaredoxinRibonucleoside diphosphate2'-Deoxyribonucleoside diphosphateGlutaredoxin disulfideH2O
Typeheavy metalamide group,carbohydrate,peptide/protein,sulfhydryl groupnucleotidenucleotideamide group,carbohydrate,disulfide bond,peptide/proteinH2O
ChEBI18248
82664




15377
PubChem23925




962
22247451
              
1pemA01UnboundUnboundUnboundUnboundUnbound 
1peoA01UnboundUnboundUnboundUnboundUnbound 
1peqA01UnboundUnboundUnboundUnboundUnbound 
1peuA01UnboundUnboundUnboundUnboundUnbound 
2bq1E01UnboundUnboundUnboundUnboundUnbound 
2bq1F01UnboundUnboundUnboundUnboundUnbound 
1pemA02UnboundUnboundUnboundUnboundUnbound 
1peoA02UnboundUnboundUnboundUnboundUnbound 
1peqA02UnboundUnboundUnboundUnboundUnbound 
1peuA02UnboundUnboundUnboundUnboundUnbound 
2bq1E02UnboundUnboundUnboundUnboundUnbound 
2bq1F02UnboundUnboundUnboundUnboundUnbound 
1pemA03UnboundUnboundUnboundUnboundUnbound 
1peoA03UnboundUnboundUnboundUnboundUnbound 
1peqA03UnboundUnboundUnboundUnboundUnbound 
1peuA03UnboundUnboundUnboundUnboundUnbound 
2bq1E03UnboundUnboundUnboundUnboundUnbound 
2bq1F03UnboundUnboundUnboundUnboundUnbound 
1pemA04UnboundUnboundUnboundUnboundUnbound 
1peoA04UnboundUnboundUnboundAnalogue:DCPUnbound 
1peqA04UnboundUnboundUnboundAnalogue:TTPUnbound 
1peuA04UnboundUnboundUnboundAnalogue:DTPUnbound 
2bq1E04UnboundUnboundUnboundAnalogue:DGTUnbound 
2bq1F04UnboundUnboundUnboundAnalogue:DGTUnbound 
1r2fABound:2x_FEUnboundUnboundUnboundUnbound 
1r2fBBound:2x_FEUnboundUnboundUnboundUnbound 
2bq1IBound:2x_FEUnboundUnboundUnboundUnbound 
2bq1JBound:2x_FEUnboundUnboundUnboundUnbound 
2r2fAAnalogue:FEOUnboundUnboundUnboundUnbound 
2r2fBAnalogue:FEOUnboundUnboundUnboundUnbound 
1kgnABound:2x_FEUnboundUnboundUnboundUnbound 
1kgnBBound:2x_FEUnboundUnboundUnboundUnbound 
1kgnCBound:2x_FEUnboundUnboundUnboundUnbound 
1kgnDBound:2x_FEUnboundUnboundUnboundUnbound 
1kgoABound:2xFE2UnboundUnboundUnboundUnbound 
1kgoBBound:2xFE2UnboundUnboundUnboundUnbound 
1kgoCBound:2xFE2UnboundUnboundUnboundUnbound 
1kgoDBound:2xFE2UnboundUnboundUnboundUnbound 
1kgpAAnalogue:2x_MNUnboundUnboundUnboundUnbound 
1kgpBAnalogue:2x_MNUnboundUnboundUnboundUnbound 
1kgpCAnalogue:2x_MNUnboundUnboundUnboundUnbound 
1kgpDAnalogue:2x_MNUnboundUnboundUnboundUnbound 
1oquABound:2x_FEUnboundUnboundUnboundUnbound 
1oquBBound:2x_FEUnboundUnboundUnboundUnbound 
1oquCBound:2x_FEUnboundUnboundUnboundUnbound 
1oquDBound:2x_FEUnboundUnboundUnboundUnbound 

Active-site residues
resource
PDB;2r1r, 3r1r & Swiss-prot;P00452 & literature [14]
pdbCatalytic residuesCofactor-binding residuescomment
           
1pemA01 
 
 
1peoA01 
 
 
1peqA01 
 
 
1peuA01 
 
 
2bq1E01 
 
 
2bq1F01 
 
 
1pemA02 
 
 
1peoA02 
 
 
1peqA02 
 
 
1peuA02 
 
 
2bq1E02 
 
 
2bq1F02 
 
 
1pemA03TYR 692;TYR 693
 
 
1peoA03TYR 692;TYR 693
 
 
1peqA03TYR 692;TYR 693
 
 
1peuA03TYR 692;TYR 693
 
 
2bq1E03TYR 692;TYR 693
 
 
2bq1F03TYR 692;TYR 693
 
 
1pemA04CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
 
 
1peoA04CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
 
disulfide bonded/oxidized form C178-C415
1peqA04CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
 
disulfide bonded/oxidized form C178-C415
1peuA04CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
 
disulfide bonded/oxidized form C178-C415
2bq1E04CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
 
disulfide bonded/oxidized form C178-C415
2bq1F04CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
 
disulfide bonded/oxidized form C178-C415
1r2fATYR 105
ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU  98;GLU 192(both Iron-1 & Iron-2)
 
1r2fBTYR 105
ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU  98;GLU 192(both Iron-1 & Iron-2)
 
2bq1ITYR 105
ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU  98;GLU 192(both Iron-1 & Iron-2)
 
2bq1JTYR 105
ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU  98;GLU 192(both Iron-1 & Iron-2)
 
2r2fATYR 105
ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU  98;GLU 192(both Iron-1 & Iron-2)
(oxidized)
2r2fBTYR 105
ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU  98;GLU 192(both Iron-1 & Iron-2)
(oxidized)
1kgnATYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(oxidized)
1kgnBTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(oxidized)
1kgnCTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(oxidized)
1kgnDTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(oxidized)
1kgoATYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(reduced)
1kgoBTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(reduced)
1kgoCTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(reduced)
1kgoDTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
(reduced)
1kgpATYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1kgpBTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1kgpCTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1kgpDTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1oquATYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1oquBTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1oquCTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 
1oquDTYR 115
ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.13360, p.13362-13368
[3]p.1387
[4]p.90-93
[7]Fig.1, p.368-369

references
[1]
PubMed ID7809142
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages12892-6
AuthorsJordan A, Pontis E, Atta M, Krook M, Gibert I, Barbe J, Reichard P
TitleA second class I ribonucleotide reductase in Enterobacteriaceae: characterization of the Salmonella typhimurium enzyme.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID98422290
PubMed ID9748343
JournalBiochemistry
Year1998
Volume37
Pages13359-69
AuthorsEriksson M, Jordan A, Eklund H
TitleStructure of Salmonella typhimurium nrdF ribonucleotide reductase in its oxidized and reduced forms.
Related PDB1r2f,2r2f
Related UniProtKBP17424
[3]
PubMed ID11802741
JournalBiochemistry
Year2002
Volume41
Pages1381-9
AuthorsHogbom M, Huque Y, Sjoberg BM, Nordlund P
TitleCrystal structure of the di-iron/radical protein of ribonucleotide reductase from Corynebacterium ammoniagenes.
Related PDB1kgn,1kgo,1kgp
[4]
PubMed ID12818204
JournalJ Mol Biol
Year2003
Volume330
Pages87-97
AuthorsUppsten M, Farnegardh M, Jordan A, Eliasson R, Eklund H, Uhlin U
TitleStructure of the large subunit of class Ib ribonucleotide reductase from Salmonella typhimurium and its complexes with allosteric effectors.
Related PDB1pem,1peo,1peq,1peu
[5]
PubMed ID15178319
JournalFEBS Lett
Year2004
Volume567
Pages179-82
AuthorsHogbom M, Nordlund P
TitleA protein carboxylate coordinated oxo-centered tri-nuclear iron complex with possible implications for ferritin mineralization.
Related PDB1oqu
[6]
PubMed ID15196041
JournalBiochemistry
Year2004
Volume43
Pages7966-72
AuthorsAndersson ME, Hogbom M, Rinaldo-Matthis A, Blodig W, Liang Y, Persson BO, Sjoberg BM, Su XD, Nordlund P
TitleStructural and mutational studies of the carboxylate cluster in iron-free ribonucleotide reductase R2.
[7]
PubMed ID16631785
JournalJ Mol Biol
Year2006
Volume359
Pages365-77
AuthorsUppsten M, Farnegardh M, Domkin V, Uhlin U
TitleThe first holocomplex structure of ribonucleotide reductase gives new insight into its mechanism of action.
Related PDB2bq1

comments
This enzyme belongs to the class I ribonucleotide reductases (RNR). The class I enzyme can be further subdivided into Ia and Ib. This entry is for the subclass Ib, whose subunits are called R1E and R2F. The class Ib enzymes are present in prokaryotes. The class Ib enzyme differs from the class Ia enzyme, by not having an overall allosteric regulation.
According to the literature [7], this enzyme catalyzes the following reactions:
(A) Electron transfer from glutaredoxin (an external donor) to the redox-active Cys709-Cys712 (disulfide) at the C-terminus of the R1E subunit.
(B) Electron transfer from the C-terminus redox-active cysteine pair to the active site redox-active Cys178-Cys415.
(C) Electron transfer from the active site redox-active cysteine pair (Cys178 & Cys415) to the substrate nucleotide.
(D) Radical formation at Tyr105 of the R2F subunit:
(E) Radical transfer from Tyr105 to the di-iron site of the R2F subunit.
(F) Radical transfer from the di-iron site to the active site Cys388, through Tyr304 of the R2F subunit and Tyr693/Tyr692 of the R1E subunit, generating a thiyl radical at Cys388.
(G) Radical reaction for the substrate nucleotide at the active site Cys388.
#####
Other classes are as follows:
Class I enzymes: M00011, M00205 (class Ia)
Clsss II enzyme (e.g. adenocylcobalamine-dependent rebonucleotide reductase from Lactobacillus leichmannii, E.C 1.17.4.2).
Class III enzyme (E.C. 1.17.4.2): M00203

createdupdated
2004-03-252009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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