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Besides the canonical pore that allows passage of cations into the cell, the TRPM3 channel has an alternative ‘omega’ permeation pathway formed by the S1–S4 region of the protein. This peripheral pore is inwardly rectifying, whereas the canonical central axis pore is outwardly rectifying.
Allosteric small-molecule inhibitors of the p53-induced oncogenic phosphatase Wip1 bind at a ‘flap’ subdomain near the catalytic site. Inhibitor GSK2830371 inhibits the phosphatase and oncogenic activities in cell lines and a xenograft tumor model.
