This study investigates the structural basis of protein function across diverse biological systems, with a focus on how atomic-level architecture governs regulation, catalysis, and disease mechanisms. Combining X-ray crystallography with biochemical and computational approaches, it integrates structural and functional data to elucidate the molecular determinants of protein activity.
The lecture is organized around three main themes. First, it presents a structural-functional analysis of germline missense variants in the Ras–MAPK signaling pathway associated with neurodevelopmental disorders, showing that these variants induce subtle, mechanistically distinct effects compared to oncogenic mutations. Second, it examines enzymes of the α/β-hydrolase fold, including haloacid dehalogenase phosphatases and haloalkane dehalogenases, revealing how active-site architecture and access tunnel dynamics shape substrate specificity and catalytic efficiency. Third, it characterizes parasite-derived protease inhibitors from the serpin and cystatin families, uncovering unique structural adaptations.
Overall, it highlights the importance of integrative structural biology in linking molecular structure to biological function.
This study was supported by the Grant Agency of the Czech Republic No. 23-07810S, the Grant Agency of the University of South Bohemia No. 04-106/2021/P, No. 04-046/2022/P, No. 04-077/2025/P, and EMBO Installation grant No. 5310.