The NEET proteins are a novel family of iron–sulfur proteins characterized by an unusual three cysteine and one histidine coordinated [2Fe–2S] cluster. Aberrant cluster release, facilitated by the breakage of the Fe–N bond, is implicated in a variety of human diseases, including cancer. Here, the molecular dynamics in the multi-microsecond timescale, along with quantum chemical calculations, on two representative members of the family (the human NAF-1 and mitoNEET proteins), show that the loss of the cluster is associated with a dramatic decrease in secondary and tertiary structure. In addition, the calculations provide a mechanism for cluster release and clarify, for the first time, crucial differences existing between the two proteins, which are reflected in the experimentally observed difference in the pH-dependent cluster reactivity. The reliability of our conclusions is established by an extensive comparison with the NMR data of the solution proteins, in part measured in this work.

中文翻译：

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NEET蛋白的[2Fe–2S]簇结合域的分子动力学模拟揭示了诱导其簇转移/释放的关键分子决定簇。

NEET蛋白是一个新的铁硫蛋白家族，其特征是具有不寻常的三个半胱氨酸和一个组氨酸配位的[2Fe-2S]簇。Fe-N键断裂促进异常簇释放，与包括癌症在内的多种人类疾病有关。在这里，在多微秒级的分子动力学以及量子化学计算，对该家族的两个代表性成员（人NAF-1和mitoNEET蛋白）进行了研究，结果表明，该簇的损失与H2O的急剧减少有关。二级和三级结构。另外，该计算提供了簇释放的机制，并首次澄清了两种蛋白质之间存在的关键差异，这在pH依赖性簇反应性的实验观察到的差异中得到反映。