Structure-Guided Modeling and Binding Studies of GABAA Receptor Subunit Beta-3

Abstract

major inhibitory GABA systems are known to take part a vital role in epilepsy, associated with excessive neuronal circuitry excitation. This excitatory action reflects seizures which result from GABA inhibitory circuit dysfunction. GABA mediates its fast inhibition through GABAA receptors by activating it and then opens the chloride channels. This opening allows chloride ions to flow into the interior of the cell which inhibits the excitability. This inhibitory action devises anticonvulsive properties as a consequence. So GABAA receptors are primary targets in the pathophysiology of epilepsy. Enhancement in the the action of GABAA receptors is the basis of epileptic seizures reduction on which many antiseizure drugs act. Modulation of GABAA receptor can be shown by many synthetic and natural compounds. Valerenic acid, a plant origin compound shows modulatory effects on GABAA receptors. In our present study, the homology model of the GABAA receptor subunit beta-3 is build and docking studies are performed with Valerenic acid. Docking analysis is done to know the binding interactions and their binding affinity. The results revealed the interacting amino acids which are involved in binding of GABAA receptor subunit beta-3 with Valerenic acid are ASP35, GLN56, PHE55, TYR120, ARG111 and TYR 54.