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首页> 外文期刊>Biochemistry >Circular dichroism and magnetic circular dichroism studies of the active site of p53R2 from human and mouse: Iron binding and nature of the biferrous site relative to other ribonucleotide reductases
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Circular dichroism and magnetic circular dichroism studies of the active site of p53R2 from human and mouse: Iron binding and nature of the biferrous site relative to other ribonucleotide reductases

机译：来自人类和小鼠的p53R2活性位点的圆二色性和磁性圆二色性研究：相对于其他核糖核苷酸还原酶的铁结合和双金属位点的性质

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Ribonucleotide reductases (RNR) catalyze the rate-limiting step in the synthesis of deoxyribonucleotides from the corresponding ribonucleotides in the synthesis of DNA. Class I RNR has two subunits: R1 with the substrate binding and active site and R2 with a stable tyrosyl radical and diiron cluster. Biferrous R2 reacts with oxygen to form the tyrosyl radical needed for enzymatic activity. A novel R2 form, p53R2, is a 351-amino acid protein induced by the "tumor suppressor gene" p53. p53R2 has been studied using a combination of circular dichroism, magnetic circular dichroism, variable-temperature variable-field MCD, and EPR spectroscopies. The active site of biferrous p53R2 in both the human (hp53R2) and mouse (mp53R2) forms is found to have one five-coordinate and one four-coordinate iron, which are weakly antiferromagnetically coupled through mu-1,3-carboxylate bridges. These spectroscopic data are very similar to those of Escherichia coli R2, and mouse R2, with a stronger resemblance to data of the former. Titrations of apo-hp53R2 and apo-mp53R2 with Fe(II) were pursued for the purpose of comparing their metal binding affinities to those of other R2s. Both p53R2s were found to have a high affinity for Fe(II), which is different from that of mouse R2 and may reflect differences in the regulation of enzymatic activity, as p53R2 is mainly triggered during DNA repair. The difference in ferrous affinity between mammalian R2 and p53R2 suggests the possibility of specific inhibition of DNA precursor synthesis during cell division.
机译：核糖核苷酸还原酶（RNR）催化DNA合成中相应的核糖核苷酸合成脱氧核糖核苷酸的限速步骤。 I类RNR具有两个亚基：R1具有底物结合和活性位点，R2具有稳定的酪氨酰基和二铁簇。双亚铁基R2与氧反应形成酶活性所需的酪氨酰自由基。一种新的R2形式，p53R2，是由“肿瘤抑制基因” p53诱导的351个氨基酸的蛋白质。使用圆二色性，磁性圆二色性，可变温度可变场MCD和EPR光谱学的组合研究了p53R2。发现在人类（hp53R2）和小鼠（mp53R2）形式中的双亚铁p53R2的活性位点具有一个五配位铁和一个四配位铁，它们通过mu-1,3-羧酸盐桥微弱地反铁磁耦合。这些光谱数据与大肠杆菌R2和小鼠R2非常相似，与前者的数据更相似。为了比较apo-hp53R2和apo-mp53R2与Fe（II）的滴定作用，目的是比较它们与其他R2的金属结合亲和力。发现两个p53R2对Fe（II）的亲和力都很高，这与小鼠R2的亲和力不同，并且可能反映了酶活性调节的差异，因为p53R2主要是在DNA修复过程中触发的。哺乳动物R2和p53R2之间的铁亲和力差异表明细胞分裂过程中DNA前体合成受到特异性抑制的可能性。

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