Global Discovery Chemistry
Basel, Switzerland
Research in the Structural and Biophysical Chemistry group focuses on understanding the structure-function relationship of interactions between biological macromolecules of medical interest and their binding partners, with an emphasis on characterizing protein-protein and protein-ligand interactions. We support projects related to the Emeryville-based Infectious Diseases area as well as global projects in other disease areas, such as oncology, in collaboration with other NIBR sites.
To study protein-ligand interactions, our lab employs solution-state biomolecular NMR as a major technique, as well as additional structural and biophysical methods established in our group such as X-ray crystallography, SPR, DSF, BLI, and light scattering. Our goal is to understand molecular recognition and ‘druggability’ at a structural level to address critical biological questions in disease. This information allows us to modulate the target function using structure-based drug design. To support drug discovery projects, we focus on hit finding, hit validation, and structural characterization, primarily in the context of fragment-based lead discovery. Besides applying and improving established ligand- and protein-observed NMR methods, we are actively involved in developing new methods and tools, e.g., expanding the application of fluorine NMR in compound screening, automated data analysis, and utilizing sparse NMR-derived structural information to define protein-ligand binding modes.
Selected Publications
Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.
Dueber EC, Schoeffler AJ, Lingel A, Elliott JM, Fedorova AV, Giannetti AM, Zobel K, Maurer B, Varfolomeev E, Wu P, Wallweber HJ, Hymowitz SG, Deshayes K, Vucic D, Fairbrother WJ.
Science. 2011 Oct 21;334(6054):376-80.
Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.
Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ.
Structure. 2009 Oct 14;17(10):1398-410.
Nucleic acid 3'-end recognition by the Argonaute2 PAZ domain.
Lingel A, Simon B, Izaurralde E, Sattler M.
Nat Struct Mol Biol. 2004 Jun;11(6):576-7.
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