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Science & Technology Concentrates

January 24, 2011
Volume 89, Number 4
p. 31

Knockout Pictures

X-ray structures of general anesthetics binding to an ion channel could aid search for new anesthetics

Carmen Drahl

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Propofol (green and red) binds at the mouth of a cavity in an algal ion channel, and desflurane (blue and red) binds deeper within the cavity. Courtesy of Pierre-Jean Corringer
Propofol (green and red) binds at the mouth of a cavity in an algal ion channel, and desflurane (blue and red) binds deeper within the cavity.

A close-up of an ion channel from blue-green algae reveals that two common anesthetics bind to it in roughly the same place (Nature, DOI: 10.1038/nature09647). This information could help researchers design new anesthetics. General anesthetics keep patients unconscious during surgeries, but it’s not clear how they work at the molecular level. Now, a team led by Pierre-Jean Corringer of France’s Pasteur Institute has determined the X-ray crystal structure of the algal channel, which resembles human acetylcholine and GABA receptors, with the anesthetics propofol and desflurane. Both molecules bind in a cavity in the membrane-spanning portion of the channel. Propofol binds at the mouth of the cavity whereas desflurane binds deeper inside. Mutating amino acids lining the binding sites affected sensitivity to the anesthetics. Ion-channel expert Sergei I. Sukharev of the University of Maryland praised the work, adding “it would be terrific if the authors introduced similar mutations into related mammalian receptors and tested them for sensitivity to propofol and desflurane.”

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2011 American Chemical Society
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