Schematic illustration of TRPM7 regulation by oxidative stress. Left: Under basal conditions, the current inhibition by Mg²⁺ binding to the high-affinity site (indicated by an orange arrow) is attenuated possibly via the interdomain interaction between the channel domain and the kinase domain. The structural integrity of the kinase domain is guaranteed by the zinc-binding motif that coordinates Zn²⁺ (indicated by brown) via C1809, C1813, H1750, and H1807. For simplicity, the low-affinity Mg²⁺-binding site that is assumed to exist in the kinase domain is not shown here. Right: Oxidative stress causes the oxidation of the cysteines (C1809 and C1813) in the zinc-binding motif, which may disrupt the interaction between the channel domain and the kinase domain and enhance the inhibition of TRPM7 by intracellular Mg²⁺.