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. 2019 Sep 20;10:972. doi: 10.3389/fphar.2019.00972

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Copyright © 2019 Shim, Brown, Singh, Singh, Fettinger, Yarov-Yarovoy and Wulff

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Rosetta Model of the wild type K_Ca3.1 channel in open state 1 with serine in position 372 (A) and of the S372R mutant (B). Hydrogen bonds are visualized in black. (C) Overlay of the Rosetta models of the S₄₅A helix/CaM N-lobe interface pocket in the wild type (yellow) and the S372R mutant shown in space fill. (D) Concentration-response curve for SKA-111 induced current activation: WT (EC₅₀ = 146 nM, 95% CI: 99–193 nM), S372R (EC₅₀ = 6.860 µM, 95% CI: 6.788–6.932 µM, P < 0.0001), S181A-L185A-S372R (EC₅₀ = 8.876 µM, 95% CI: 8.652–9.100 µM, P < 0.0001). Data points are mean ± S.D. from 3–5 independent cells/recordings.