CEA, Nuclear Energy Division, Radiochemistry Process Department, SCPS/LILA, 30207 Bagnols sur Cèze, France.
Chemistry. 2010 Jan 25;16(4):1378-87. doi: 10.1002/chem.200901209.
The impact of actinides on living organisms has been the subject of numerous studies since the 1950s. From a general point of view, these studies show that actinides are chemical poisons as well as radiological hazards. Actinides in plasma are assumed to be mainly complexed to transferrin, the iron carrier protein. This paper casts light on the uptake of actinides(IV) (thorium, neptunium, plutonium) by transferrin, focusing on the pH dependence of the interaction and on a molecular description of the cation binding site in the protein. Their behavior is compared with that of iron(III), the endogenous transferrin cation, from a structural point of view. Complementary spectroscopic techniques (UV/Vis spectrophotometry, microfiltration coupled with gamma spectrometry, and X-ray absorption fine structure) have been combined in order to propose a structural model for the actinide-binding site in transferrin. Comparison of our results with data available on holotransferrin suggests some similarities between the behavior of Fe(III) and Np(IV)/Pu(IV)/ Np(IV) is not complexed at pH <7, whereas at pH approximately 7.4 complexation can be regarded as quantitative. This pH effect is consistent with the in vivo transferrin "cycle". Pu(IV) also appears to be quantitatively bound by apotransferrin at around pH approximately 7.5, whereas Th(IV) was never complexed under our experimental conditions. EXAFS data at the actinide edge have allowed a structural model of the actinide binding site to be elaborated: at least one tyrosine residue could participate in the actinide coordination sphere (two for iron), forming a mixed hydroxo-transferrin complex in which actinides are bound with transferrin both through An-tyrosine and through An--OH bonds. A description of interatomic distances is provided.
自 20 世纪 50 年代以来，钍、镎、钚等锕系元素对生物体的影响一直是众多研究的主题。从一般观点来看，这些研究表明锕系元素既是化学毒物，又是放射性危害物。人们认为，等离子体中的锕系元素主要与转铁蛋白（铁载体蛋白）形成复合物。本文重点研究了转铁蛋白对锕系元素（IV）（钍、镎、钚）的摄取，关注相互作用的 pH 值依赖性，并对蛋白质中阳离子结合位点进行分子描述。从结构角度比较了它们与内源性转铁蛋白阳离子铁（III）的行为。为了提出转铁蛋白中锕系元素结合位点的结构模型，我们结合了互补的光谱技术（紫外/可见分光光度法、与伽马谱学相结合的微过滤法和 X 射线吸收精细结构）。将我们的结果与完整转铁蛋白的数据进行比较，表明 Fe(III) 和 Np(IV)/Pu(IV)之间的行为存在一些相似之处。在 pH<7 时，Np(IV) 不与转铁蛋白形成复合物，而在 pH 约为 7.4 时，复合物可以被认为是定量的。这种 pH 效应与体内转铁蛋白“循环”一致。在 pH 约为 7.5 时，Pu(IV) 似乎也被脱铁转铁蛋白定量结合，而在我们的实验条件下，Th(IV) 从未与转铁蛋白形成复合物。在锕系元素边缘的 EXAFS 数据允许构建一个锕系元素结合位点的结构模型：至少一个酪氨酸残基可能参与锕系元素的配位球（铁为两个），形成一个混合的羟基-转铁蛋白复合物，其中锕系元素通过 An-酪氨酸和 An-OH 键与转铁蛋白结合。提供了原子间距离的描述。
