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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sg-ntu-dr.10356-690992023-02-28T18:31:56Z Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II Lim, Pei Yiing Pär Nordlund School of Biological Sciences DRNTU::Science 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. Master of Science 2016-10-28T08:03:26Z 2016-10-28T08:03:26Z 2016 Thesis http://hdl.handle.net/10356/69099 en 100 p. application/pdf |
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DRNTU::Science Lim, Pei Yiing Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II |
| description |
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. |
| author2 |
Pär Nordlund |
| author_facet |
Pär Nordlund Lim, Pei Yiing |
| format |
Theses and Dissertations |
| author |
Lim, Pei Yiing |
| author_sort |
Lim, Pei Yiing |
| title |
Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II |
| title_short |
Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II |
| title_full |
Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II |
| title_fullStr |
Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II |
| title_full_unstemmed |
Structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase II |
| title_sort |
structural and functional studies of leukemia-associated mutations in human cytosolic 5'-nucleotidase ii |
| publishDate |
2016 |
| url |
http://hdl.handle.net/10356/69099 |
| _version_ |
1759853163833196544 |