Towards a Better Understanding of Kinases in Health and Disease. Development of New Methods for Characterization of Protein Dynamics and Structure.

This application asks for the support for three different projects. The first two projects are directed at biophysical characterization of two different kinases with the ultimate goals of designing an inhibitor for the calcium dependent kinase (CDPK) of the parasite P. falciparum and for understanding the regulation of the kinase activity of human EphB2. In addition of answering specific scientific questions, the second project concerns NMR methodology and building competence in the area of Structural Biology at Linköping University. This study will adopt NMR spectroscopy characterize CDPKs from P. falciparum and related parasites. The researcher will initially assign the NMR signals to specific nuclei and study the binding of calcium to the protein, then solve the solution structure for the regulatory region of P. falciparum and use that knowledge to search for inhibitors. A related project concerns understanding of the regulation of the kinase EphB2, which is implicated in cancers. The researcher detected a millisecond dynamics in the protein and want to test the hypothesis that the catalytically competent state involves an excited state by combining this knowledge with a comparison of structures of the wild type protein and a mutant designed to stabilize the excited state. Additionally the researcher want to develop NMR methods for studying protein dynamics and structures of excited states like folding intermediates.

Project details

Genetics and Genomics

Jan 2013 — Dec 2016

$461,411

Sweden