Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II

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 par...

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Bibliographic Details
Main Author: Lim, Pei Yiing
Other Authors: Pär Nordlund
Format: Theses and Dissertations
Language:English
Published: 2016
Subjects:
Online Access:http://hdl.handle.net/10356/69099
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.