New structural data made it possible to decipher the mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein
Calcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human cancers. That is why the development of efficient channel blockers is very important for biomedicine. At the same time, despite their pharmacological value, natural channel blockers have been previously largely neglected. Researchers from the Laboratory of Biomolecular Modeling of IBCh RAS together with colleagues from Columbia University (New York, USA) have identified structural aspects of the interaction of TRPV6 with the natural phytoestrogen genistein, which has previously shown itself in clinical studies as a blocker of cell invasion and metastasis. Using a state-of-the art biophysical approach combining cryo-EM, electrophysiology, calcium imaging, protein engineering, and molecular modeling methods, the team of scientists managed to show that genistein, binding to TRPV6, works as a pore blocker that changes the structure of the activation gate of the ion channel. The described molecular mechanism opens up new possibilities in the development of antitumor drugs. The results are published in Nature Communications. Learn more
may 23, 2023