Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383, Wrocław, Poland.
Institute of Health Sciences, University of Opole, Katowicka 68, 45-060, Opole, Poland.
Sci Rep. 2022 Jan 10;12(1):425. doi: 10.1038/s41598-021-04197-5.
Membrane environment often has an important effect on the structure, and therefore also on the coordination mode of biologically relevant metal ions. This is also true in the case of Cu(II) coordination to amylin analogues-rat amylin, amylin, pramlintide and Ac-pramlintide, which offer N-terminal amine groups and/or histidine imidazoles as copper(II) anchoring sites. Complex stabilities are comparable, with the exception of the very stable Cu(II)-amylin, which proves that the presence of the amylin C-terminus lowers its affinity for copper(II); although not directly involved, its appropriate arrangement sterically prevents early metal binding. Most interestingly, in membrane-mimicking solution, the Cu(II) affinities of amylin analogues are lower than the ones in water, probably due to the crowding effect of the membrane solution and the fact that amide coordination occurs at higher pH, which happens most likely because the α-helical structure, imposed by the membrane-mimicking solvent, prevents the amides from binding at lower pH, requiring a local unwinding of the α-helix.
膜环境通常对结构有重要影响，因此也对生物相关金属离子的配位模式有重要影响。这同样适用于 Cu(II)与淀粉样肽类似物-大鼠淀粉样肽、淀粉样肽、普兰林肽和 Ac-普兰林肽的配位情况，它们提供 N-末端胺基和/或组氨酸咪唑作为 Cu(II)的锚定位点。配合物稳定性相当，除了非常稳定的 Cu(II)-淀粉样肽外，这证明了淀粉样肽 C 末端的存在降低了其对铜(II)的亲和力；尽管没有直接参与，但它的适当排列在空间上阻止了早期金属结合。最有趣的是，在模拟膜的溶液中，淀粉样肽类似物的 Cu(II)亲和力低于水中的亲和力，这可能是由于膜溶液的拥挤效应以及酰胺配位在较高 pH 下发生的事实，这很可能是因为由模拟膜溶剂施加的α-螺旋结构阻止了酰胺在较低 pH 下结合，需要局部解开α-螺旋。
