Department of Physics, Michigan Technological University, Houghton, MI 49931, USA.
Phys Chem Chem Phys. 2010 Oct 7;12(37):11390-7. doi: 10.1039/c003568h. Epub 2010 Aug 16.
We study in silico possible mechanisms by that the A629P mutant of ATP7A causes Menkes Disease. Our results indicate that the mutation does not have appreciable affects on the stability of copper-bound states but rather destabilizes the characteristic end-to-end β-sheet. In this way, the mutation presumably increases the probability for aggregation and/or degradation leading to decreased concentration of the monomer.
我们通过计算机模拟研究了 ATP7A 的 A629P 突变导致 Menkes 病的可能机制。我们的结果表明，该突变对铜结合状态的稳定性没有明显影响，但会使特征性的端到端β-折叠失稳。这样，突变可能会增加聚集和/或降解的概率，导致单体浓度降低。
