Gaggelli Elena, Kozlowski Henryk, Valensin Daniela, Valensin Gianni
Department of Chemistry, University of Siena, Via Aldo Moro, Siena 53100, Italy.
Mol Biosyst. 2005 May;1(1):79-84. doi: 10.1039/b419413f. Epub 2005 Mar 8.
The interaction of copper(II) with histidine containing peptides has recently acquired renewed interest following the established link between abnormal protein behaviour in neurodegenerative processes and unpaired copper homeostasis. Five peptide sequences taken from the amyloid precursor protein and the prion protein were considered. Addition of paramagnetic Cu(II) ions to solutions of such peptides was not found to severely affect the appearance of NMR spectra, thus limiting the usual approach for structural determination. Exchange kinetics was shown to play a major role in determining the observed paramagnetic spin-lattice relaxation rates. Two independent methods were suggested for evaluating the exchange rates of His-containing peptides from the copper-coordination sphere and to calculate copper-proton distances. In such a way NMR was demonstrated to have the potential of providing detailed structures of the Cu(II)-peptide complexes in solution.
鉴于神经退行性过程中异常蛋白质行为与不成对铜稳态之间已确立的联系，铜（II）与含组氨酸肽的相互作用最近重新引起了人们的关注。研究考虑了从淀粉样前体蛋白和朊病毒蛋白中提取的五个肽序列。向此类肽的溶液中添加顺磁性铜（II）离子并未发现会严重影响核磁共振谱的外观，从而限制了通常用于结构测定的方法。结果表明，交换动力学在决定观察到的顺磁自旋晶格弛豫速率方面起主要作用。提出了两种独立的方法来评估含组氨酸肽从铜配位球中的交换速率，并计算铜-质子距离。通过这种方式，核磁共振被证明有潜力提供溶液中铜（II）-肽复合物的详细结构。
