This image shows a small fly. The image is from the Wikimedia Commons.
Ion channels in the nervous system are important targets for pesticides. Understanding the structure of the channels is important for the identification of novel binding sites. The structure and function of a potassium ion channel from fruit flies was revealed by researchers at the Max Planck Institute of Molecular Physiology in Germany. Their newly obtained insights show the differences between human and insect channels, explain how compounds affect the channel, and propose new target sites for drugs. The research could help pesticide manufacturers design new drugs that kill pests without affecting other animals.
The Slowpoke potassium channels in the fruit fly are huge and complex, and they are able to transport vital potassium ion through it. They are the brains and muscles of all animals and are responsible for completing many tasks. The importance of targeting Slowpoke with newly developed insecticides is shown by the essential roles of the potassium channels. The risk of not aiming properly is always there. "Ideally, you want the pesticides to be specific to the pest insect, avoiding drugs that are toxic for humans, or other animals, such as birds, rodents and beneficial insects like bees," says the lead author of the book.
Scientists need high-resolution structures of the ion channels in order to design drugs that are specific for pests. The structures of the open and closed states of the human proteins were compared with the structures of the open and closed states of the human proteins by the researchers. The difference between human and insect channels is very small.
The map shows the channel for drug discovery.
The RCK2 pocket is a specific site that has differences between humans and flies. The gating ring is at the bottom of the channel. The gating ring sits inside the cell and picks up calcium ion when it's abundant. The RCK2 pocket changes shape as it moves between states. It is a perfect target for small molecule to block the channel. Other less insect-specific drug target sites were pinpointed by scientists. The S6 pocket could be used to lock the channel. "We are giving pharmaceutical scientists with a detailed map of the potassium channel, which they can use to make better, highlyselective insecticides."
The researchers solved the issues of the channel's cryo-EM structures with two compounds. The small molecule in the S6 pocket is the neurotoxin verruculogen. The channel is locked in the closed state by Verruculogen. emodepside is a drug used against gastrointestinal worms in cats and dogs. It is difficult for potassium to go through the channel in an optimal way because it acts differently as an additional passing filter. "It's important to understand how the ligands can manipulate the channel," says Raunser.
The small molecule modulation of the Drosophila slo channel was studied by the team. There is a DOI titled " 10.1038/s41467-021-27435-w".
Nature Communications is a journal.
There are new channels to target pest insects that were found on December 14.
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