Department of Inorganic and Analytical Chemistry, University of Szeged, Szeged, Hungary.
Metallomics. 2011 Dec;3(12):1331-9. doi: 10.1039/c1mt00138h. Epub 2011 Oct 31.
A de novo designed dodecapeptide (HS), inspired by the metal binding loops of metal-responsive transcriptional activators, was synthesized. The aim was to create a model system for structurally promiscuous and intrinsically unstructured proteins, and explore the effect of metal ions on their structure and dynamics. The interaction with Cd(II) was investigated by UV, synchrotron radiation CD, (1)H NMR, and perturbed angular correlation (PAC) of γ-rays spectroscopy, pH-potentiometry, and molecular modelling. The peptide mainly displays characteristics of random coil in the CD spectra, and the molecular dynamics simulations demonstrate that it is unstructured with transient and varying helical content. The spectroscopic studies revealed the formation of loop structures with the coordination of the two Cys-thiolates close to each end of the HS peptide, in the presence of one equivalent of Cd(II) per ligand. The imidazole moiety from histidine is also bound to Cd(II) at neutral pH and above. In the presence of 0.5 equivalent of Cd(II) per HS metal bridged structures with e.g. CdS(2)N(2) and possibly CdS(4) coordination geometries are formed above pH ~6. In an equilibrium of several co-existing species the peptide is exchanging between a number of structures also in its metal ion bound state(s), as indicated by NMR and PAC data.
受金属响应转录激活因子金属结合环启发，设计了一种新的十二肽（HS）。目的是创建一个结构混杂和固有无结构蛋白质的模型系统，并探索金属离子对其结构和动力学的影响。通过紫外光谱、同步辐射圆二色性（CD）、（1）H NMR 和γ射线受扰角关联（PAC）光谱、pH 电位滴定和分子建模研究了与 Cd(II) 的相互作用。该肽在 CD 光谱中主要表现为无规卷曲的特征，分子动力学模拟表明它是无结构的，具有瞬态和变化的螺旋含量。光谱研究表明，在每个配体存在一个当量的 Cd(II)的情况下，形成了具有两个 Cys-硫醇末端配位的环结构。在中性 pH 值及以上条件下，组氨酸的咪唑部分也与 Cd(II)结合。在 0.5 当量 Cd(II)存在下，HS 金属桥联结构在 pH 值约 6 以上形成，例如 CdS(2)N(2)和可能的 CdS(4)配位几何结构。在几种共存物种的平衡中，如 NMR 和 PAC 数据所示，肽在其金属离子结合态之间交换多种结构。
