Revealing an Internal Stabilization Deficiency in the DNA Polymerase β K289M Cancer Variant through the Combined Use of Chemical Biology and X-ray Crystallography.

ABSTRACT: The human DNA polymerase (pol) β cancer variant K289M has altered polymerase activity in vitro, and the structure of wild-type pol β reveals that the K289 side chain contributes to a network of stabilizing interactions in a C-terminal region of the enzyme distal to the active site. Here, we probed the capacity of the K289M variant to tolerate strain introduced within the C-terminal region and active site. Strain was imposed by making use of a dGTP analogue containing a CF₂ group substitution for the β-γ bridging oxygen atom. The ternary complex structure of the K289M variant displays an alteration in the C-terminal region, whereas the structure of wild-type pol β is not altered in the presence of the dGTP CF₂ analogue. The alteration in the K289M variant impact

SUBMITTER: Batra VK 

PROVIDER: S-EPMC7263314 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature