PubMed 25734225
Referenced in: none
Automatically associated channels: Kv1.2
Title: In Silico Identification of PAP-1 Binding Sites in the Kv1.2 Potassium Channel.
Authors: Christian Jorgensen, Leonardo Darré, Kenno Vanommeslaeghe, Kiyoyuki Omoto, David Pryde, Carmen Domene
Journal, date & volume: Mol. Pharm., 2015 Mar 16 , ,
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25734225
Abstract
Voltage-gated potassium channels of the Kv1 family play a crucial role in the generation and transmission of electrical signals in excitable cells affecting neuronal and cardiac activities. Small-molecule blockage of these channels has been proposed to occur via a cooperative mechanism involving two main blocking sites: the inner-pore site located below the selectivity filter, and a side-pocket cavity located between the pore and the voltage sensor. Using 0.5 μs molecular dynamics simulation trajectories complemented by docking calculations, the potential binding sites of the PAP-1 (5-(4-phenoxybutoxy)psoralen) blocker to the crystal structure of Kv1.2 channel have been studied. The presence of both mentioned blocking sites at Kv1.2 is confirmed, adding evidence in favor of a cooperative channel blockage mechanism. These observations provide insight into drug modulation that will guide further developments of Kv inhibitors.