About our group
The research in Strisovsky lab is focused on biological membranes and enzymatic catalysis occurring in their context. We are studying the ubiquitous intramembrane proteases of the rhomboid family and the mechanistic aspects of their functions relevant for biological signaling, membrane protein biogenesis and homeostasis. In our work we integrate the tools of membrane biochemistry, enzymology and structural biology to understand how rhomboid proteases recognise and select substrates, and employ methods of quantitative proteomics, cell biology and genetics to uncover molecular basis of rhomboid functions in organisms. We are an international group and we are always eager to consider motivated students and postdocs who would like to join us. If interested, contact Kvido Strisovsky.
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Targeting the Membrane-Embedded Rhomboid Protease GlpG: A Multimodal Strategy for Inhibitor Discovery and Mechanistic Insight
Angewandte Chemie International Edition 2026: Early View
Rhomboid proteases, a class of intramembrane proteases characterized by a Ser-His catalytic dyad, have recently emerged as promising therapeutic targets. While inhibitors for soluble serine proteases have been extensively studied, the spectrum of potent rhomboid protease inhibitor chemotypes is limited to active-site targeted nucleophiles. To address this limitation, we conducted a high-throughput screen of over 68,000 compounds targeting the E. coli rhomboid protease GlpG, using a fluorescent liposome-based assay. A selection of 326 inhibitory compounds was evaluated in a subsequent IC50 screen against two variants of GlpG (core domain and full length), a soluble serine protease (chymotrypsin), as well as the human mitochondrial rhomboid PARL. Of these, the selective inhibitory effects of 2 compounds and their analogues on GlpG were confirmed through further biochemical and biophysical characterisation, molecular docking, and solid-state NMR spectroscopy. This study paves the way for…
Extensive targeting of chemical space at the prime side of ketoamide inhibitors of rhomboid proteases by branched substituents empowers their selectivity and potency
European Journal of Medicinal Chemistry 275: 116606 (2024)
Maintenance of organellar protein homeostasis by ER-associated degradation and related mechanisms
Molecular Cell 81 (12): 2507-2519 (2021)
Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease
EMBO Journal 39 (10): e102935 (2020)
General and Modular Strategy for Designing Potent, Selective, and Pharmacologically Compliant Inhibitors of Rhomboid Proteases
Cell Chemical Biology 24 (12): 1523-1536 (2017)
