P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of Ivermectin and Zinc Allosteric Modulation.

ABSTRACT: Protein allosteric modulation is a pillar of metabolic regulatory mechanisms; this concept has been extended to include ion channel regulation. P2XRs are ligand-gated channels activated by extracellular ATP, sensitive to trace metals and other chemicals. By combining in silico calculations with electrophysiological recordings, we investigated the molecular basis of P2X4R modulation by Zn(II) and ivermectin, an antiparasite drug currently used in veterinary medicine. To this aim, docking studies, molecular dynamics simulations and non-bonded energy calculations for the P2X4R in the apo and holo states or in the presence of ivermectin and/or Zn(II) were accomplished. Based on the crystallized Danio rerio P2X4R, the rat P2X4R, P2X2R, and P2X7R structures were modeled, to determi

SUBMITTER: Latapiat V 

PROVIDER: S-EPMC5737101 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature