Mapping a novel positive allosteric modulator binding site in the central vestibule region of human P2X7.

ABSTRACT: P2X7 receptors are important in the regulation of inflammatory responses and immune responses to intracellular pathogens such as Mycobacterium tuberculosis and Toxoplasma gondii. Enhancement of P2X7 receptor responses may be useful in pathogen clearance particularly in individuals with defective microbial killing mechanisms. Ginsenosides from Panax ginseng have been discovered to act as positive allosteric modulators of P2X7. Here we describe a novel modulator binding site identified by computational docking located in the central vestibule of P2X7 involving S60, D318, and L320 in the lower body β-sheets lining the lateral portals. Potentiation of ATP-mediated responses by ginsenosides CK and Rd caused enhanced ionic currents, Ca²⁺ influx and YOPRO-1 uptake in stably transfected

SUBMITTER: Bidula SM 

PROVIDER: S-EPMC6397193 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature