On-Cell Saturation Transfer Difference NMR Spectroscopy on Ion Channels: Characterizing Negative Allosteric Modulator Binding Interactions of P2X7.

ABSTRACT: P2X7 receptors are important drug targets involved in pathologies ranging from psychiatric disorders to cancer. Being membrane embedded receptors, they are more challenging for structural characterization, and at present, we only have a small number of X-ray and cryo-EM structures for P2X7 bound to antagonists. We demonstrate that saturation transfer difference (STD) NMR on live mammalian cells (on-cell STD NMR) overexpressing P2X7 receptors allows further structural insight on the complexes of P2X7 with two potent negative allosteric modulators, namely, AZ10606120 and JNJ-47965567, via the determination of the binding epitope mapping of the interactions, e.g., the main region of contact between the ligand and the binding pocket. This approach, reported for the first time on membrane-embed

SUBMITTER: Monaco S 

PROVIDER: S-EPMC12426935 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature