RNR (M1M2) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin)

Stable Identifier
R-HSA-111742
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
NDP + reduced glutaredoxin => dNDP + oxidized glutaredoxin + H2O
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Ribonucleotide reductase (RNR (M1M2)) catalyzes the reduction of adenine, guanine, cytidine, and uridine ribonucleoside 5'-diphosphates (NDPs) to form the corresponding deoxyribonucleoside 5'-diphosphates, coupled to the oxidation of glutaredoxin (Eklund et al. 2001). The enzyme complex is cytosolic (Pontarin et al. 2008). The form of ribonucleotide reductase annotated here is a tetramer of two large (M1) and two small (M2) subunits (Zhou et al. 2005). Expression of RNR (M1M2) is confined to the S phase of the cell cycle by restriction of the expression of the M1 gene and by degradation of the M1 gene product at the end of S phase. The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).

The reducing equivalents needed for ribonucleotide reductase activity can be provided by either of two small proteins, glutaredoxin or thioredoxin (Holmgren 1989; Sun et al. 1998; Zahedi Avval & Holmgren 2009). Both are re-reduced with NADPH as the donor of reducing equivalents. The relative contributions of glutaredoxin and thioredoxin in vivo are unknown.

Literature References
PubMed ID Title Journal Year
18997010 Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage

Pontarin, G, Fijolek, A, Pizzo, P, Ferraro, P, Rampazzo, C, Pozzan, T, Thelander, L, Reichard, PA, Bianchi, V

Proc. Natl. Acad. Sci. U.S.A. 2008
9677297 The NMR solution structure of human glutaredoxin in the fully reduced form

Sun, C, Berardi, MJ, Bushweller, JH

J Mol Biol 1998
19176520 Molecular mechanisms of thioredoxin and glutaredoxin as hydrogen donors for Mammalian s phase ribonucleotide reductase

Zahedi Avval, F, Holmgren, A

J. Biol. Chem. 2009
2668278 Thioredoxin and glutaredoxin systems

Holmgren, A

J Biol Chem 1989
10884394 Cross-talk between the allosteric effector-binding sites in mouse ribonucleotide reductase

Reichard, PA, Eliasson, R, Ingemarson, R, Thelander, L

J Biol Chem 2000
11796141 Structure and function of the radical enzyme ribonucleotide reductase

Eklund, H, Uhlin, U, Farnegardh, M, Logan, DT, Nordlund, P

Prog Biophys Mol Biol 2001
16373698 A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases

Zhou, B, Shao, J, Su, L, Yuan, YC, Qi, C, Shih, J, Xi, B, Chu, B, Yen, Y

Mol Cancer Ther 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ribonucleoside-diphosphate reductase activity, glutaredoxin disulfide as acceptor of RNR (M1M2) [cytosol]
Physical Entity
Activity
This event is regulated
Negatively by
Positively by
Orthologous Events
Created