DB code: M00204

CATH domain 1.10.-.- :
1.10.-.- :
3.90.244.10 : Catalytic domain
3.90.188.10 : Catalytic domain
1.10.620.20 : Ribonucleotide Reductase, subunit A Catalytic domain
E.C. 1.17.4.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.620.20 : Ribonucleotide Reductase, subunit A S00028 M00151 M00205
3.90.188.10 : M00205
3.90.244.10 : M00205

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q08698 Ribonucleoside-diphosphate reductase 2 subunit alpha
EC 1.17.4.1
Ribonucleotide reductase 2
R1E protein
NP_461733.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
PF02867 (Ribonuc_red_lgC)
PF00317 (Ribonuc_red_lgN)
PF08343 (RNR_N)
[Graphical View]
P17424 Ribonucleoside-diphosphate reductase 2 subunit beta
EC 1.17.4.1
Ribonucleotide reductase 2
R2F protein
NP_461734.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
PF00268 (Ribonuc_red_sm)
[Graphical View]
O69274
Ribonucleotide reductase subunit R2F
PF00268 (Ribonuc_red_sm)
[Graphical View]

KEGG enzyme name
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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q08698 RIR3_SALTY 2''-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin. Tetramer of two alpha and two beta subunits (By similarity).
P17424 RIR4_SALTY 2''-deoxyribonucleoside diphosphate + thioredoxin disulfide + H(2)O = ribonucleoside diphosphate + thioredoxin. Tetramer of two alpha and two beta subunits (By similarity). Binds 2 iron ions per subunit.
O69274 O69274_CORAM

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism
MAP00240 Pyrimidine metabolism
MAP00480 Glutathione metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00023 C07292 C03723 C04232 C07293 C00001
E.C.
Compound Iron Glutaredoxin Ribonucleoside diphosphate 2'-Deoxyribonucleoside diphosphate Glutaredoxin disulfide H2O
Type heavy metal amide group,carbohydrate,peptide/protein,sulfhydryl group nucleotide nucleotide amide group,carbohydrate,disulfide bond,peptide/protein H2O
ChEBI 18248
 82664
 18248
 82664
 		15377
 15377
PubChem 23925
 23925
 		22247451
 962
 22247451
 962
1pemA01 Unbound Unbound Unbound Unbound Unbound
1peoA01 Unbound Unbound Unbound Unbound Unbound
1peqA01 Unbound Unbound Unbound Unbound Unbound
1peuA01 Unbound Unbound Unbound Unbound Unbound
2bq1E01 Unbound Unbound Unbound Unbound Unbound
2bq1F01 Unbound Unbound Unbound Unbound Unbound
1pemA02 Unbound Unbound Unbound Unbound Unbound
1peoA02 Unbound Unbound Unbound Unbound Unbound
1peqA02 Unbound Unbound Unbound Unbound Unbound
1peuA02 Unbound Unbound Unbound Unbound Unbound
2bq1E02 Unbound Unbound Unbound Unbound Unbound
2bq1F02 Unbound Unbound Unbound Unbound Unbound
1pemA03 Unbound Unbound Unbound Unbound Unbound
1peoA03 Unbound Unbound Unbound Unbound Unbound
1peqA03 Unbound Unbound Unbound Unbound Unbound
1peuA03 Unbound Unbound Unbound Unbound Unbound
2bq1E03 Unbound Unbound Unbound Unbound Unbound
2bq1F03 Unbound Unbound Unbound Unbound Unbound
1pemA04 Unbound Unbound Unbound Unbound Unbound
1peoA04 Unbound Unbound Unbound Analogue:DCP Unbound
1peqA04 Unbound Unbound Unbound Analogue:TTP Unbound
1peuA04 Unbound Unbound Unbound Analogue:DTP Unbound
2bq1E04 Unbound Unbound Unbound Analogue:DGT Unbound
2bq1F04 Unbound Unbound Unbound Analogue:DGT Unbound
1r2fA Bound:2x_FE Unbound Unbound Unbound Unbound
1r2fB Bound:2x_FE Unbound Unbound Unbound Unbound
2bq1I Bound:2x_FE Unbound Unbound Unbound Unbound
2bq1J Bound:2x_FE Unbound Unbound Unbound Unbound
2r2fA Analogue:FEO Unbound Unbound Unbound Unbound
2r2fB Analogue:FEO Unbound Unbound Unbound Unbound
1kgnA Bound:2x_FE Unbound Unbound Unbound Unbound
1kgnB Bound:2x_FE Unbound Unbound Unbound Unbound
1kgnC Bound:2x_FE Unbound Unbound Unbound Unbound
1kgnD Bound:2x_FE Unbound Unbound Unbound Unbound
1kgoA Bound:2xFE2 Unbound Unbound Unbound Unbound
1kgoB Bound:2xFE2 Unbound Unbound Unbound Unbound
1kgoC Bound:2xFE2 Unbound Unbound Unbound Unbound
1kgoD Bound:2xFE2 Unbound Unbound Unbound Unbound
1kgpA Analogue:2x_MN Unbound Unbound Unbound Unbound
1kgpB Analogue:2x_MN Unbound Unbound Unbound Unbound
1kgpC Analogue:2x_MN Unbound Unbound Unbound Unbound
1kgpD Analogue:2x_MN Unbound Unbound Unbound Unbound
1oquA Bound:2x_FE Unbound Unbound Unbound Unbound
1oquB Bound:2x_FE Unbound Unbound Unbound Unbound
1oquC Bound:2x_FE Unbound Unbound Unbound Unbound
1oquD Bound:2x_FE Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;2r1r, 3r1r & Swiss-prot;P00452 & literature [14]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1pemA01
1peoA01
1peqA01
1peuA01
2bq1E01
2bq1F01
1pemA02
1peoA02
1peqA02
1peuA02
2bq1E02
2bq1F02
1pemA03 TYR 692;TYR 693
1peoA03 TYR 692;TYR 693
1peqA03 TYR 692;TYR 693
1peuA03 TYR 692;TYR 693
2bq1E03 TYR 692;TYR 693
2bq1F03 TYR 692;TYR 693
1pemA04 CYS 178;ASN 386;CYS 388;GLU 390;CYS 415
1peoA04 CYS 178;ASN 386;CYS 388;GLU 390;CYS 415 disulfide bonded/oxidized form C178-C415
1peqA04 CYS 178;ASN 386;CYS 388;GLU 390;CYS 415 disulfide bonded/oxidized form C178-C415
1peuA04 CYS 178;ASN 386;CYS 388;GLU 390;CYS 415 disulfide bonded/oxidized form C178-C415
2bq1E04 CYS 178;ASN 386;CYS 388;GLU 390;CYS 415 disulfide bonded/oxidized form C178-C415
2bq1F04 CYS 178;ASN 386;CYS 388;GLU 390;CYS 415 disulfide bonded/oxidized form C178-C415
1r2fA TYR 105 ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU 98;GLU 192(both Iron-1 & Iron-2)
1r2fB TYR 105 ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU 98;GLU 192(both Iron-1 & Iron-2)
2bq1I TYR 105 ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU 98;GLU 192(both Iron-1 & Iron-2)
2bq1J TYR 105 ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU 98;GLU 192(both Iron-1 & Iron-2)
2r2fA TYR 105 ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU 98;GLU 192(both Iron-1 & Iron-2) (oxidized)
2r2fB TYR 105 ASP 67;HIS 101(Iron-1);GLU 158;HIS 195(Iron-2);GLU 98;GLU 192(both Iron-1 & Iron-2) (oxidized)
1kgnA TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (oxidized)
1kgnB TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (oxidized)
1kgnC TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (oxidized)
1kgnD TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (oxidized)
1kgoA TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (reduced)
1kgoB TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (reduced)
1kgoC TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (reduced)
1kgoD TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2) (reduced)
1kgpA TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1kgpB TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1kgpC TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1kgpD TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1oquA TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1oquB TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1oquC TYR 115 ASP 77;HIS 111(Iron-1);GLU 168;HIS 205(Iron-2);GLU 108;GLU 202(both Iron-1 & Iron-2)
1oquD TYR 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
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 7809142
Journal Proc Natl Acad Sci U S A
Year 1994
Volume 91
Pages 12892-6
Authors Jordan A, Pontis E, Atta M, Krook M, Gibert I, Barbe J, Reichard P
Title A second class I ribonucleotide reductase in Enterobacteriaceae: characterization of the Salmonella typhimurium enzyme.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
Medline ID 98422290
PubMed ID 9748343
Journal Biochemistry
Year 1998
Volume 37
Pages 13359-69
Authors Eriksson M, Jordan A, Eklund H
Title Structure of Salmonella typhimurium nrdF ribonucleotide reductase in its oxidized and reduced forms.
Related PDB 1r2f 2r2f
Related UniProtKB P17424
[3]
Resource
Comments
Medline ID
PubMed ID 11802741
Journal Biochemistry
Year 2002
Volume 41
Pages 1381-9
Authors Hogbom M, Huque Y, Sjoberg BM, Nordlund P
Title Crystal structure of the di-iron/radical protein of ribonucleotide reductase from Corynebacterium ammoniagenes.
Related PDB 1kgn 1kgo 1kgp
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12818204
Journal J Mol Biol
Year 2003
Volume 330
Pages 87-97
Authors Uppsten M, Farnegardh M, Jordan A, Eliasson R, Eklund H, Uhlin U
Title Structure of the large subunit of class Ib ribonucleotide reductase from Salmonella typhimurium and its complexes with allosteric effectors.
Related PDB 1pem 1peo 1peq 1peu
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 15178319
Journal FEBS Lett
Year 2004
Volume 567
Pages 179-82
Authors Hogbom M, Nordlund P
Title A protein carboxylate coordinated oxo-centered tri-nuclear iron complex with possible implications for ferritin mineralization.
Related PDB 1oqu
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 15196041
Journal Biochemistry
Year 2004
Volume 43
Pages 7966-72
Authors Andersson ME, Hogbom M, Rinaldo-Matthis A, Blodig W, Liang Y, Persson BO, Sjoberg BM, Su XD, Nordlund P
Title Structural and mutational studies of the carboxylate cluster in iron-free ribonucleotide reductase R2.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16631785
Journal J Mol Biol
Year 2006
Volume 359
Pages 365-77
Authors Uppsten M, Farnegardh M, Domkin V, Uhlin U
Title The first holocomplex structure of ribonucleotide reductase gives new insight into its mechanism of action.
Related PDB 2bq1
Related UniProtKB

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

Created Updated
2004-03-25 2009-02-26