J Am Chem Soc 2021 Mar 24;143(11):4311-4318. Epub 2021 Feb 24.
School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
A deficiency of Ca fluxes arising from dysfunctional voltage-gated calcium channels has been associated with a list of calcium channelopathies such as epilepsy, hypokalemic periodic paralysis, episodic ataxia, etc. Apart from analyzing the pathogenic channel mutations, understanding how the channel regulates the ion conduction would be instructive to the treatment as well. In the present work, in relating the free energetics of Ca transport to the calcium channel, we demonstrate the importance of bridging Ca hydration waters, which form hydrogen bonds with channel -COO and -C═O groups and enable a long-distance effect on the Ca permeation. Read More