We warmly invite you to participate in the SCIENTÍFika series of seminars organised by the User Office at MAX IV
Where – Virtual format by Zoom call https://lu-se.zoom.us/j/61349123545
When – Monday 13:45 CET
Format – 30 minutes of presentation followed by 15 minutes of discussion, chaired by MAX IV staff
Monday 9 May 2022, 13:45 CET
Application of Fragment Screening at BioMAX for development of specific inhibitors of Deoxyhypusine Synthase (DHS)
Speaker: Dr Piotr Wilk, Structural Biology Core Facility, Jagiellonian University Krakow (Poland)
Host: Dr Tobias Krojer, BioMAX beamline scientist
Keywords: Fragment screening, DHS, inhibitor, parasite, x-ray crystallography, enzyme
Hypusination is a unique posttranslational modification present in only one protein – a translation factor eIF5A. Its presence directly affects activity of ribosomes and indirectly a plethora of cellular functions and its absence is linked to several human disorders. The modification is introduced by two consecutive enzymatic reactions catalyzed by DeoxyHypusine Synthase (DHS) and DeOxyHypusine Hydroxylase (DOHH). It was demonstrated that DHS is crucial for hypusination and the enzyme was suggested as a target in anticancer therapies, however we currently lack specific inhibitors to further investigate the role of DHS in healthy or defective cells.
Fragment Screening (FS) is an approach to develop specific inhibitors based on testing of binding of hundreds of relatively simple chemical compounds to the target protein of interest. Such approach has many advantages compared to traditional high-throughput screening. Various biophysical techniques were used in FS campaigns, however crystallographic approach has unique advantages as it not only identifies “hits” but also provides information on their mode of binding.
We have recently used FragMAX platform and employing BioMAX we have collected hundreds of diffraction data sets unraveling many new ligands that will aid development of specific inhibitors of DHS.
We look forward to see you online and hope you enjoy the talk!