Biophysical Examination of the Dual Roles of Choline Kinase Alpha
Kall, Stefanie Lynne
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Choline kinase alpha (ChoK) is an enzyme that is of interest to cancer biologists due to its upregulation in tumour cells and its role in maintaining aberrant cell behaviour. In order to develop better drug targets for this protein, we use crystallography and other biophysical methods to elucidate two different roles it plays in the cell. First, it is an enzyme, responsible for the production of phosphocholine, which induces malignant transformation and is necessary for the formation of cell membranes. We use X-ray crystallography to examine a unique inhibitor binding mode for this enzyme, adopted by a Phase II chemotherapeutic molecule. Second, ChoK has an additional role as a binding partner to endothelial growth factor receptor (EGFR), an interaction that is mediated by the oncoprotein c-Src. We use surface plasmon resonance (SPR) and X-ray crystallography to examine how the SH3 domain of c-Src and the N-terminal region of ChoK interact. Together, our biophysical work illustrates the multifaceted impact a single protein can have on the cell environment.
Subjectcholine kinase alpha