Baicalein Acts against Candida albicans by Targeting Eno1 and Inhibiting Glycolysis
Liping Li, Hui Lu, Xuan Zhang, Malcolm Whiteway, Hao Wu, Shan-Lun Tan, Jianye Zang, Shujuan Tian, Cheng Zhen, Xianlei Meng, Wanqian Li, Dazhi Zhang, Min Zhang, Yuanying Jiang
Abstract
Baicalein (BE) is a promising antifungal agent which has been well characterized, but its target protein is still undiscovered. The protein Eno1 plays a crucial role in the survival of Candida albicans. However, there are few antifungal agents which inhibit the functions of Eno1. Here, we found that BE can function against Candida albicans by disrupting glycolysis through targeting Eno1 and inhibiting its function. We further solved the crystal structure of C. albicans Eno1(CaEno1) and predicted that the primary binding site of BE on CaEno1 is between amino acids D261 and W274, with D263, S269, and K273 playing critical roles in the interaction with BE. Our findings will be helpful to get specific small-molecule inhibitors of CaEno1 and open the way for the development of new antifungal therapeutics targeted at inhibiting glycolysis.