Unknown

Dataset Information

0

Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4.


ABSTRACT: Recently a novel inhibitor of Wnt signaling was discovered. The compound, WIKI4, was found to act through tankyrase inhibition and regulate ?-catenin levels in many cancer cell lines and human embryonic stem cells. Here we confirm that WIKI4 is a high potency tankyrase inhibitor and that it selectively inhibits tankyrases over other ARTD enzymes tested. The binding mode of the compound to tankyrase 2 was determined by protein X-ray crystallography to 2.4 Å resolution. The structure revealed a novel binding mode to the adenosine subsite of the donor NAD(+) binding groove of the catalytic domain. Our results form a structural basis for further development of potent and selective tankyrase inhibitors based on the WIKI4 scaffold.

SUBMITTER: Haikarainen T 

PROVIDER: S-EPMC3675114 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4.

Haikarainen Teemu T   Venkannagari Harikanth H   Narwal Mohit M   Obaji Ezeogo E   Lee Hao-Wei HW   Nkizinkiko Yves Y   Lehtiö Lari L  

PloS one 20130606 6


Recently a novel inhibitor of Wnt signaling was discovered. The compound, WIKI4, was found to act through tankyrase inhibition and regulate β-catenin levels in many cancer cell lines and human embryonic stem cells. Here we confirm that WIKI4 is a high potency tankyrase inhibitor and that it selectively inhibits tankyrases over other ARTD enzymes tested. The binding mode of the compound to tankyrase 2 was determined by protein X-ray crystallography to 2.4 Å resolution. The structure revealed a no  ...[more]

Similar Datasets

| S-EPMC3515623 | biostudies-literature
| S-EPMC3465688 | biostudies-literature
| S-EPMC3215855 | biostudies-literature
| S-EPMC5980575 | biostudies-literature
| S-EPMC9712121 | biostudies-literature
| S-EPMC2819028 | biostudies-literature
| S-EPMC2925040 | biostudies-literature
| S-EPMC4475917 | biostudies-literature
| S-EPMC3143158 | biostudies-literature
| S-EPMC7366343 | biostudies-literature