Summary
This technical report presents the first reported structure of a G-Protein Coupled Receptor (GPCR) solved using diffraction data collected on a home-lab X-ray system, specifically the D8 VENTURE METALJET. The structure of the human Orexin-1 StaR® was determined at a resolution of 2.77 Å in a monoclinic space group. The report outlines the challenges associated with GPCR structure determination, emphasizing their conformational heterogeneity and instability. It details the significance of StaR technology, which enhances the thermostability of GPCRs, facilitating their crystallization. The report also discusses the advantages of using in-house systems for crystallography, including rapid data collection and real-time decision-making for medicinal chemists. The findings indicate that the D8 VENTURE METALJET can effectively support structure-based drug design (SBDD) pipelines, particularly for GPCRs, by providing high-quality data from single crystals. The successful determination of the Orexin-1 receptor structure demonstrates the potential of this approach for future drug discovery efforts.
