Sevoflurane-induced structural changes in a four-alpha-helix bundle protein.
The mechanisms whereby volatile general anesthetics reversibly alter protein function in the central nervous system remain obscure. Using three different spectroscopic approaches, evidence is presented that binding of the modern general anesthetic sevoflurane to the hydrophobic core of a model four-alpha-helix bundle protein results in structural changes. Aromatic residues in the hydrophobic core reorient into new environments upon anesthetic binding, and the protein as a whole becomes less dynamic and exhibits structural tightening. Comparable structural changes in the predicted in vivo protein targets, such as the gamma-aminobutyric acid type A receptor and the N-methyl-D-aspartate receptor, may underlie some, or all, of the behavioral effects of these widely used clinical agents.
Pidikiti
Ravindernath
R
Department of Anesthesiology and Critical Care Medicine, and Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhang
Tao
T
Mallela
Krishna M G
KM
Shamim
Mohammad
M
Reddy
Konda S
KS
Johansson
Jonas S
JS
D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008738:Methyl Ethers / Q000494:pharmacology*; D017433:Protein Structure, Secondary / Q000187:drug effects; D018079:Receptors, GABA / Q000737:chemistry* / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000378:metabolism*; D000077149:Sevoflurane; D013050:Spectrometry, Fluorescence
D008738:Methyl Ethers; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D000077149:Sevoflurane