Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II
Lim, Pei Yiing
Date of Issue2016-10-28
School of Biological Sciences
NT5C2 relapse-associated mutations, K359Q and R367Q, are correlated with large gains in their enzymatic profiles. Crystal structures obtained in this study provide insights to the allosteric regulation mechanism of the enzyme by the disorder-to-order transition of a regulatory helix, which forms part of the active site. In addition, the mutant enzymes possess an increased basal level of activity and sensitivity to activation by effectors. In this study, the structural aspects of how each mutation potentially gains an advantage over the wild-type protein is revealed, with supporting evidence from biochemical and biophysical assays.