Calcium Competitive Inhibition of Langerin by Thiazolopyrimidinones.

ABSTRACT: C-Type lectins are a large family of carbohydrate-binding proteins. Langerin is a member of this family and is expressed by Langerhans cells, involved in pathogen recognition and innate immune activation, making it a target for small-molecule modulation in immunology and infectious diseases. We previously identified thiazolopyrimidinones as a series of allosteric inhibitors, but the underlying mechanism remained unclear. In this study, ⁴³Ca NMR demonstrated that these fragments induce Ca²⁺ release from the receptor. Our ITC data suggested a competitive relationship between inhibitors and Ca²⁺, which was further validated by ¹⁹F NMR spectroscopy showing inhibition of carbohydrate binding. Surprisingly, the fragment binding site was found to be loc

SUBMITTER: Ning Y 

PROVIDER: S-EPMC7618453 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature