Data from: Deconstruction of an African folk medicine uncovers a novel molecular strategy for therapeutic potassium channel activation
De Silva, Angele M., University of California, Irvine
Manville, Rían W., University of California, Irvine
Abbott, Geoffrey W., University of California, Irvine
Published Nov 15, 2018 on Dryad.
Cite this dataset
De Silva, Angele M.; Manville, Rían W.; Abbott, Geoffrey W. (2018). Data from: Deconstruction of an African folk medicine uncovers a novel molecular strategy for therapeutic potassium channel activation [Dataset]. Dryad. https://doi.org/10.5061/dryad.97p31jr
A third of the global population relies heavily upon traditional or folk medicines, such as the African shrub Mallotus oppositifolius. Here, we used pharmacological screening and electrophysiological analysis in combination with in silico docking and site-directed mutagenesis to elucidate the effects of M. oppositifolius constituents on KCNQ1, a ubiquitous and influential cardiac and epithelial voltage-gated potassium (Kv) channel. Two components of the M. oppositifolius leaf extract, mallotoxin (MTX) and 3-ethyl-2-hydroxy-2-cyclopenten-1-one (CPT1), augmented KCNQ1 current by negative shifting its voltage dependence of activation. MTX was also highly effective at augmenting currents generated by KCNQ1 in complexes with native partners KCNE1 or SMIT1; conversely, MTX inhibited KCNQ1-KCNE3 channels. MTX and CPT1 activated KCNQ1 by hydrogen bonding to the foot of the voltage sensor, a previously unidentified drug site which we also find to be essential for MTX activation of the related KCNQ2/3 channel. The findings elucidate the molecular mechanistic basis for modulation by a widely used folk medicine of an important human Kv channel and uncover novel molecular approaches for therapeutic modulation of potassium channel activity.
De Silva-Manville et al 2018 Supplementary Tables
Supplementary tables describing functional effects of M. oppositifolius leaf extract components on KCNQ1 channels, alone and with regulatory proteins. Effects of the leaf extract components on mutant KCNQ1 and KCNQ2/3 channels are also described.
De Silva-Manville et al Repository Data 9_11_18.pdf