Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4.
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 selectiv...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762361/?tool=EBI |
| _version_ | 1818700961730789376 |
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| author | Teemu Haikarainen Harikanth Venkannagari Mohit Narwal Ezeogo Obaji Hao-Wei Lee Yves Nkizinkiko Lari Lehtiö |
| author_facet | Teemu Haikarainen Harikanth Venkannagari Mohit Narwal Ezeogo Obaji Hao-Wei Lee Yves Nkizinkiko Lari Lehtiö |
| author_sort | Teemu Haikarainen |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-12-17T15:13:16Z |
| format | Article |
| id | doaj.art-d65d152848a14c07afbd50647aa37410 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T15:13:16Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d65d152848a14c07afbd50647aa374102022-12-21T21:43:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6540410.1371/journal.pone.0065404Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4.Teemu HaikarainenHarikanth VenkannagariMohit NarwalEzeogo ObajiHao-Wei LeeYves NkizinkikoLari LehtiöRecently 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 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762361/?tool=EBI |
| spellingShingle | Teemu Haikarainen Harikanth Venkannagari Mohit Narwal Ezeogo Obaji Hao-Wei Lee Yves Nkizinkiko Lari Lehtiö Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. PLoS ONE |
| title | Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. |
| title_full | Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. |
| title_fullStr | Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. |
| title_full_unstemmed | Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. |
| title_short | Structural basis and selectivity of tankyrase inhibition by a Wnt signaling inhibitor WIKI4. |
| title_sort | structural basis and selectivity of tankyrase inhibition by a wnt signaling inhibitor wiki4 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762361/?tool=EBI |
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