Minimum structural requirement for an inhalational anesthetic binding site on a protein target.

J S Johansson; R G Eckenhoff

doi:10.1016/0304-4165(95)00187-5

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Minimum structural requirement for an inhalational anesthetic binding site on a protein target.

J S Johansson·R G Eckenhoff

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Abstract

The present study makes use of direct photoaffinity labeling and fluorescence and circular dichroism spectroscopy to examine the interaction of the inhalational anesthetic halothane with the uncharged alpha-helical form of poly(L-lysine) over a range of chain lengths. Halothane bound specifically to long chain homopolymers (190 to 1060 residues), reaching a stable stoichiometry of 1 halothane to 160 lysine residues in polymers longer than 300 residues. Halothane bound only non-specifically to an alpha-helical 30 residue polymer and to all of the polymers in their charged, random coil form. The data suggest that halothane binding is a function of supersecondary structure whereby intramolecular helix-helix clusters form in the longer polymers, resulting in the creation of confined hydrophobic domains. Circular dichroism spectroscopy cannot demonstrate changes in poly(L-lysine) secondary structure at any chain length with up to 12 mM halothane, suggesting that extensive hydrogen bond disruption by the anesthetic does not occur.

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Affinity Labels Anesthetics, Inhalation Anilino Naphthalenesulfonates Binding Sites Circular Dichroism Fluorescent Dyes Protein Binding Protein Structure, Secondary Spectrometry, Fluorescence Journal Article Research Support, U.S. Gov't, P.H.S.

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J S Johansson, R G Eckenhoff. 1996-05-21. Minimum structural requirement for an inhalational anesthetic binding site on a protein target.. https://doi.org/10.1016/0304-4165(95)00187-5

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