Article
Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia.
Cancer cell - 9 Jul 2018
Dieck Chelsea L, Tzoneva Gannie, Forouhar Farhad, Carpenter Zachary, Ambesi-Impiombato Alberto, Sánchez-Martín Marta, Kirschner-Schwabe Renate, Lew Scott, Seetharaman Jayaraman, Tong Liang, Ferrando Adolfo A
Abstract excerpt
Activating mutations in the cytosolic 5'-nucleotidase II gene NT5C2 drive resistance to 6-mercaptopurine in acute lymphoblastic leukemia. Here we demonstrate that constitutively active NT5C2 mutations K359Q and L375F reconfigure the catalytic center for substrate access and catalysis in the absence of allosteric activator. In contrast, most relapse-associated mutations, which involve the arm segment and residues...
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