RNR (M1M2B) reduces nucleotide diphosphates to deoxynucleotide diphosphates (glutaredoxin)

Ribonucleotide reductase (RNR (M1M2B)) 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 (M2B) subunits (Shao et al. 2004; Zhou et al. 2005). M2B protein is stable throughout the cell cycle, unlike M2, and is induced by TP53 (Guittet et al. 2001; Tanaka et al. 2000). The RNR (M1M2B) complex can thus provide dNDPs for DNA repair in interphase and quiescent cells. Studies of mitochondrial instability in cells from patients deficient in M2 protein indicate that RNR (M1M2B) likewise provides dNDPs for mitochondrial DNA replication (Pontarin et al. 2012). The overall activity of the enzyme is regulated allosterically: ATP binding is stimulatory while dATP binding is inhibitory (Reichard et al. 2000).<p>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.

核糖核苷酸还原酶（RNR，M1M2B型）催化腺嘌呤、鸟嘌呤、胞嘧啶和尿嘧啶核糖核苷5'-二磷酸（NDPs）的还原，形成相应的脱氧核糖核苷5'-二磷酸，此过程与谷氧还蛋白（Eklund等，2001年）的氧化作用偶联。该酶复合物位于细胞质中（Pontarin等，2008年）。在此标注的核糖核苷酸还原酶形式是由两个大型（M1）和两个小型（M2B）亚基组成的四聚体（Shao等，2004年；Zhou等，2005年）。与M2不同，M2B蛋白在整个细胞周期中保持稳定，并可由TP53诱导（Guittet等，2001年；Tanaka等，2000年）。因此，RNR（M1M2B）复合物可为间期和静止细胞中的DNA修复提供dNDPs。研究显示，M2蛋白缺乏的细胞中存在线粒体不稳定，这表明RNR（M1M2B）同样可为线粒体DNA复制提供dNDPs（Pontarin等，2012年）。酶的整体活性通过变构调节：ATP结合具有促进作用，而dATP结合具有抑制作用（Reichard等，2000年）。核糖核苷酸还原酶活性所需的还原当量可由两种小蛋白之一提供，即谷氧还蛋白或硫氧还蛋白（Holmgren，1989年；Sun等，1998年；Zahedi Avval & Holmgren，2009年）。这两种蛋白均以NADPH作为还原当量的供体进行再还原。然而，在体内，谷氧还蛋白和硫氧还蛋白的相对贡献尚不明确。