NMR application in fragmentbased screening against TDP43 Tandem RRM and in dynamics of hADK2

Abstract

The advances in solution nuclear magnetic resonance (NMR) spectroscopy allowed the bacterial Adenylate Kinases dynamics to be observed with detail. However, nothing is known on conformational changes and dynamics of human Adenylate kinases. We have used the NMR relaxation dispersion (CPMG) to detect the hADK2 excited-state conformations exchanging with the ground state in the timescale of microsecond to millisecond. We also labeled hADK2 with lanthanide-chelating peptides, which paves way for the following experimental observation of Pseudocontact Shifts (PCSs) of excited-states in slow exchanging with the ground-state.