​Human Hematopoietic Prostaglandin D₂ Synthase (H-PGDS) plays a role in both allergic and inflammatory diseases such as asthmatic anaphylaxis and mastocytosis making it a potential target for selective inhibitor development. Herein we describe our continued investigation of the structural characteristics and distinct binding mechanisms of the H-PGDS with inhibitors. This study aims to evaluate a SAR series of inhibitors containing an amide or imidazole linkers in parallel with mutational analysis of H-PGDS through thermal shift assay, X-ray crystallography, and Surface Plasmon Resonance (SPR) experiments. Additionally, identification of H-PGDS key interactions and conformational changes related to the reduced glutathione (GSH) cofactor in the active site as well as the first crystal structure of H-PGDS with the natural substrate provide further insight into the design of human H-PGDS inhibitors.  

To cite this poster: Muzzarelli, K.., Assar, Z., Barrett, S., et al. Structural and Mutational Investigation of Human Hematopoietic Prostaglandin D₂ Synthase and Inhibitors. Poster presented at: 17th Annual Drug Discovery Chemistry Conference; April 18-21, 2022.