Protein dynamics and substrate recognition of human blood group glycosyltransferases

点击翻译按钮获取中文摘要

It is now recognized that human blood group glycosyltransferases A (GTA) and B (GTB) are under allosteric control of donor and acceptor substrates. Based on our previous findings, we advance the hypothesis that this allosteric control can only be fully understood when a causative connection to protein dynamics is made. Therefore, we suggest studying the protein dynamics of GTA and GTB employing NMR experiments. In parallel, we will resume isothermal titration calorimetry (ITC) experiments using novel inhibitors that interfere with the loop movement of GTA and GTB. Because of the size (70 kDa) of the target proteins we will focus on 13C-methyl labeling techniques and methyl-TROSY based NMR experiments. We will link NMR data on protein dynamics with thermodynamic data to test our hypothesis and uncover novel principles of how human blood group glycosyltransferases operate.