Chemoproteomic Profiling of <i>C. albicans</i> for Characterization of Antifungal Kinase Inhibitors.

ABSTRACT: Candida albicans is a major cause of systemic candidiasis, a severe fungal infection with a ∼40% mortality rate. Yck2, a casein kinase 1 (CK1) in C. albicans, is targeted by antifungal inhibitors YK-I-02 (YK) and MN-I-157 (MN). Using multiplexed inhibitor beads and mass spectrometry (MIB/MS), the selectivity of these inhibitors was determined across the fungal kinome. The MIB matrix captured 89% of C. albicans protein kinases, revealing that YK and MN selectively engage three CK1 homologues (Yck2, Yck22, and Hrr25) and a human p38α homologue (Hog1). Chemoproteomics using a custom MN-kinobead confirmed the remarkable fungal kinome selectivity. To identify new Yck2 inhibitors with selectivity over Hog1, 13 human CK1 inhibitors were screened, leading to the discovery of a

SUBMITTER: Shirley DJ 

PROVIDER: S-EPMC11997987 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature