Study reveals how drug molecules bind in channels between neighboring cells, changing intercellular communication.
Researchers have gained new knowledge of how drugs bind to connexin molecules. These molecules form channels that allow neighbouring cells to send direct messages to one another. Dysfunctions of these channels are involved in neurological and cardiac diseases. The new understanding of how drugs bind and act on them should help develop therapies to treat such conditions.
Such channels are created from proteins known as connexins. Six connexins situated in the cell membrane create a hemichannel; this hemichannel joins with a hemichannel in a neighbouring cell to create a two-way channel. The team studied Cx36 bound to the antimalarial drug mefloquine . The drug is known to act on the parasites that cause malaria when they enter the blood stream from infected mosquitos. However, research has indicated that the mefloquine also binds to Cx36 in our cells, potentially explaining some of the well-known severe neuropsychiatric side effects of the drug.
"Our study shows how a drug molecule lands in the pore of the channel and, through our simulations, gives a plausible explanation for how the drug inhibits the channel," says Volodymyr Korkhov, group leader at PSI and associate professor at the ETH Zurich, who led the study."This is relevant not only to Cx36, but to the wider question of connexin -- drug interactions."
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