The effects of mutation and inhibitor binding on Abl kinase conformation by hydrogen deuterium exchange mass spectrometry

摘要

HX MS reveals the effects of inhibitor binding to Abl tyrosine kinase. The HX MS experiments on wt Abl core and mutants indicated that some regions of the protein are more solvent exposed than others. Importantly, no structure was detected for the Ncap in solution which implies that the Ncap is highly mobile and that this region of the Abl core displays an unordered conformation. Conformational changes between the wt and T315I, indicated that this mutation not only affects the conformation and dynamics of the regions near the mutation site, but also affects more distant regions of the protein, such as the SH3 domain.