Conveners
Biocrystallography: Drug Design
- Martina Schäfer (Nuvisan ICB GmbH)
We determined high resolution structures of human GCH1 and GCH1-GFRP complexes by cryoEM and X-ray crystallography and studied the mechanisms of allosteric regulation by biophysical methods. Inhibition of the enzymatic activity, a drug discovery target in the field of pain disorders, is not a result of hindrance of substrate binding, but rather a consequence of accelerated substrate binding kinetics.
The selenoprotein GPX4 is a potential cancer drug target. Inhibitors covalently target the active site selenocysteine. Co-crystallization with covalent inhibitors initially failed, most likely due to heterogenous covalent modification. A mass spec-based approach to monitor cysteine modification, together with a surface cysteine mutation, enabled the structure determination of GPX4 with the...
An efficient fragment screening pipeline was set up for a global player from pharmaceutical industry. 1000 crystals were prepared at NUVISAN ICB's high-throughput crystallography platform. Beamline P14 at EMBL Hamburg was chosen for data collection and MOLOX performed this service here. Data processing and structure determination was done by the client. More than 87% of the crystals yielded a...
Macromolecular crystallography (MX) can identify compounds like fragments in their 3D structural context of the protein target, in enhanced through-put. At the MX beamlines at BESSY II, a workflow including dedicated tools, efficient compound libraries and convenient software solutions was established and optimized to provide for efficient screening. Developments like the F2X libraries, the...