General anesthetic binding mode via hydration with weak affinity and molecular discrimination: General anesthetic dissolution in interfacial water of the common binding site of GABA_A receptor.

ABSTRACT: The GABA_A receptor (GABA_AR) is a target channel for the loss of awareness of general anesthesia. General anesthetic (GA) spans a wide range of chemical structures, such as monatomic molecules, barbital acids, phenols, ethers, and alkanes. GA has a weak binding affinity, and the affinity has a characteristic that correlates with the solubility in olive oil rather than the molecular shape. The GA binding site of GABA_AR is common to GAs and exists in the transmembrane domain of the GABA_AR intersubunit. In this study, the mechanism of GA binding, which allows binding of various GAs with intersubunit selectivity, was elucidated from the hydration analysis of the binding site. Regardless of the diverse GA chemical structures, a strong correlation was o

SUBMITTER: Seto T 

PROVIDER: S-EPMC10941959 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature