Publication Abstract from PubMed
Recently a novel inhibitor of Wnt signaling was discovered. The compound, WIKI4, was found to act through tankyrase inhibition and regulate beta-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 A 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.
Structural Basis and Selectivity of Tankyrase Inhibition by a Wnt Signaling Inhibitor WIKI4.,Haikarainen T, Venkannagari H, Narwal M, Obaji E, Lee HW, Nkizinkiko Y, Lehtio L PLoS One. 2013 Jun 6;8(6):e65404. doi: 10.1371/journal.pone.0065404. Print 2013. PMID:23762361[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
