Glutathione-glutaredoxin is an efficient electron donor system for mammalian p53R2–R1-dependent ribonucleotide reductase

S‐Denitrosylation by the C‐Terminal Swinging Arm of R1 Subunit: A Novel Mechanism to Restore Ribonucleotide Reductase Activity

“…Thus, several RNR inhibitors have been used as anticancer and antiviral agents. Homodimers of R1 and R2 subunits assemble to form a heterodimeric active tetramer, called RNR complex [15–24] . Interestingly, Rofougaran et al.…”

“…found that the ATP/dATP‐induced R1 oligomers (hexamers) can interact with the R2 dimer to form an enzymatically active RNR complex [25] . The R1 subunit contains the active site thiols and allosteric sites; while the R2 subunit carries a stable tyrosyl free radical required for RNR catalysis [26–31] …”

“…It has been found that the Trx system plays a crucial role in protecting cells against both oxidative and nitrosative stress. The Trx system has been characterized to act as the electron donor for ribonucleotide reductase (RNR) which catalyzes the biosynthesis of deoxyribonucleotides from ribonucleotides to support DNA synthesis [16,17] . RNR over‐expression facilitates faster DNA synthesis and rapid cell replication leading to the development of malignancy and cancer.…”

“…It has been proposed that macrophage‐derived nitric oxide inhibits RNR in cancer cells and electron paramagnetic resonance spectroscopy experiments showed that this is due to NO‐mediated quenching of the tyrosyl free radical of R2 subunit [26–31] . Later, Roy et al.…”

Structure–activity relationship and mechanism of four monostilbenes with respect to ferroptosis inhibition

“…The Fe 3+ -reducing assay is a readout of the electron-donating potential, which affects the antioxidant potential as well as the inhibition of ferroptosis. 14,15,[51][52][53] However, electron donation is always accompanied by proton donation in cells. 54,55 The net result of electron and proton donation is generally equivalent to that of whole hydrogen donation.…”