Speaker
Description
Jörg Standfuss
representing collaborators at PSI Center for Life Sciences, PSI Center for Photon Science, LeadXpro AG, Institute for Advanced Chemistry of Catalonia, Stanford Cancer Institute, SLAC National Accelerator Laboratory, and University of Zurich
Abstract:
The advent of next-generation synchrotrons and X-ray free-electron lasers enables time-resolved structural biology at atomic resolution and femtosecond time resolution. At the Swiss Light Source (SLS), the Swiss X-ray Free Electron Laser (SwissFEL), and the Linac Coherent Light Source (LCLS), we use photoactive azobenzene compounds to trigger and follow drug–protein interaction dynamics in real time.
I will present time-resolved studies of the light-switchable drug candidate azo-combretastatin A4, tracking the process from the initial photochemical event on the femtosecond timescale to ligand release from tubulin on the millisecond timescale. Extending this approach to G protein–coupled receptors (GPCRs), we used photoswitchable compounds to follow ligand dissociation from the adenosine A2A receptor and the metabotropic glutamate receptor 5 (mGlu5). We further show how a photopharmacological compound can act as an efficacy switch, modulating β2-adrenergic receptor activity from within the binding pocket. These time-resolved structural snapshots provide new input for computational studies and for understanding protein–ligand interaction dynamics in important drug targets.
| Scientific Topics | Biology |
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