Yiqing Wei, Zhuoya Yu, Lili Wang, Xiaojing Li, Na Li, Qinru Bai, Yuhang Wang, Renjie Li, Yufei Meng, Hao Xu, Xianping Wang, Yanli Dong, Zhuo Huang, Xuejun Cai Zhang, Yan Zhao
The voltage-gated calcium channel CaV 1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of CaV 1.2 are involved in brain and heart diseases. Pharmacological inhibition of CaV 1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of CaV 1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6II , S6III , and S6IV helices and forms extensive hydrophobic interactions with CaV 1...
March 30, 2024: Nature Communications