The lipid/protein interface as xenobiotic target site: kinetic analysis of the nicotinic acetylcholine receptor.
Membrane proteins are known to be solvated and functionally activated by a fixed number of lipid molecules whose multiple binding can be described by Adair-type binding equations. Lipophilic xenobiotics such as general anesthetics may act by competitive displacement of protein-bound lipids. A kinetic equation is now presented for various binding stoichiometries of lipid and xenobiotic, and microscopic binding constants of anesthetics and organic solvents are derived from two independent assay systems for the enhancement of agonist binding to the nicotinic acetylcholine receptor. These constants lead to the first available free energy estimate (-6.4 kcal/mol) for the binding of membrane lipid to an integral membrane protein.
Walcher
S
S
Institute of Biomathematics and Biometry and the Institute of Biochemical Plant Pathology, GSF-National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
Altschuh
J
J
Sandermann
H
H
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D007700:Kinetics; D008024:Ligands; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013816:Thermodynamics; D014101:Torpedo
D000777:Anesthetics; D008024:Ligands; D008563:Membrane Lipids; D008565:Membrane Proteins; D011978:Receptors, Nicotinic