Structural changes in a four-alpha-helix bundle protein following sevoflurane binding

A molecular understanding of volatile general anesthetic mechanisms of action will ultimately require high-resolution structural descriptions of anesthetic-protein complexes. Structural changes in proteins following anesthetic binding have been technically difficult to detect, but presumably underlie many of the resulting reversible alterations in protein function. Using three different spectroscopic approaches, evidence is presented that binding of a modern general anesthetic to the four-α-helix bundle (Aα2-L1M/L38M)2 results in conformational changes in the target. Comparable structural changes in in vivo central nervous system protein targets may underlie some, or all, of the behavioral effects of these widely used clinical agents.