Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Chemistry. 2011 May 2;17(19):5393-403. doi: 10.1002/chem.201001931. Epub 2011 Apr 4.
With a view on protein-nucleic acid interactions in the presence of metal ions we studied the "simple" mixed-ligand model systems containing histamine (Ha), the metal ions Ni(2+), Cu(2+), or Zn(2+) (M(2+)), and the nucleotides adenosine 5'-triphosphate (ATP(4-)) or uridine 5'-triphosphate (UTP(4-)), which will both be referred to as nucleoside 5'-triphosphate (NTP(4-)). The stability constants of the ternary M(NTP)(Ha)(2-) complexes were determined in aqueous solution by potentiometric pH titrations. We show for both ternary-complex types, M(ATP)(Ha)(2-) and M(UTP)(Ha)(2-), that intramolecular stacking between the nucleobase and the imidazole residue occurs and that the stacking intensity is approximately the same for a given M(2+) in both types of complexes: The formation degree of the intramolecular stacks is estimated to be 20 to 50%. Consequently, in protein-nucleic acid interactions imidazole-nucleobase stacks may well be of relevance. Furthermore, the well-known formation of macrochelates in binary M(2+) complexes of purine nucleotides, that is, the phosphate-coordinated M(2+) interacts with N7, is confirmed for the M(ATP)(2-) complexes. It is concluded that upon formation of the mixed-ligand complexes the M(2+)-N7 bond is broken and the energy needed for this process corresponds to the stability differences determined for the M(UTP)(Ha)(2-) and M(ATP)(Ha)(2-) complexes. It is, therefore, possible to calculate from these stability differences of the ternary complexes the formation degrees of the binary macrochelates: The closed forms amount to (65±10)%, (75±8)%, and (31±14) % for Ni(ATP)(2-), Cu(ATP)(2-), and Zn(ATP)(2-), respectively, and these percentages agree excellently with previous results obtained by different methods, confirming thus the internal validity of the data and the arguments used in the evaluation processes. Based on the overall results it is suggested that M(ATP)(2-) species, when bound to an enzyme, may exist in a closed macrochelated form only, if no enzyme groups coordinate directly to the metal ion.
考虑到金属离子存在时蛋白质-核酸相互作用，我们研究了含有组氨酸 (Ha)、金属离子 Ni(2+)、Cu(2+) 或 Zn(2+) (M(2+)) 以及核苷酸腺苷 5'-三磷酸 (ATP(4-)) 或尿苷 5'-三磷酸 (UTP(4-)) 的“简单”混合配体模型系统，这两种核苷酸都将被称为核苷 5'-三磷酸 (NTP(4-))。通过电位 pH 滴定法在水溶液中确定了三元 M(NTP)(Ha)(2-)配合物的稳定常数。我们表明，对于两种类型的三元配合物，M(ATP)(Ha)(2-)和 M(UTP)(Ha)(2-)，核碱基和咪唑残基之间发生分子内堆积，并且在两种类型的配合物中，给定 M(2+)的堆积强度大致相同：分子内堆积的形成程度估计为 20% 至 50%。因此，在蛋白质-核酸相互作用中，咪唑-核碱基堆积很可能是相关的。此外，嘌呤核苷酸的二元 M(2+)配合物中形成的大环螯合物，即磷酸配位的 M(2+)与 N7 相互作用，也得到了 M(ATP)(2-)配合物的证实。因此，可以得出结论，在形成混合配体配合物时，M(2+)-N7 键被打破，并且该过程所需的能量对应于为 M(UTP)(Ha)(2-)和 M(ATP)(Ha)(2-)配合物确定的稳定性差异。因此，可以从三元配合物的这些稳定性差异计算出二元大环螯合物的形成程度：对于 Ni(ATP)(2-)、Cu(ATP)(2-) 和 Zn(ATP)(2-)，封闭形式分别为 (65±10)%、(75±8)% 和 (31±14)%，这些百分比与以前用不同方法获得的结果非常吻合，从而证实了数据和评估过程中使用的论点的内部有效性。基于总体结果，建议当 M(ATP)(2-) 物种与酶结合时，如果没有酶基团直接与金属离子配位，则其可能仅以封闭的大环螯合形式存在。
