RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site
Oncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-021-24316-0 |
| _version_ | 1831730030017773568 |
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| author | Katarzyna Z. Haza Heather L. Martin Ajinkya Rao Amy L. Turner Sophie E. Saunders Britta Petersen Christian Tiede Kevin Tipping Anna A. Tang Modupe Ajayi Thomas Taylor Maia Harvey Keri M. Fishwick Thomas L. Adams Thembaninkosi G. Gaule Chi H. Trinh Matthew Johnson Alexander L. Breeze Thomas A. Edwards Michael J. McPherson Darren C. Tomlinson |
| author_facet | Katarzyna Z. Haza Heather L. Martin Ajinkya Rao Amy L. Turner Sophie E. Saunders Britta Petersen Christian Tiede Kevin Tipping Anna A. Tang Modupe Ajayi Thomas Taylor Maia Harvey Keri M. Fishwick Thomas L. Adams Thembaninkosi G. Gaule Chi H. Trinh Matthew Johnson Alexander L. Breeze Thomas A. Edwards Michael J. McPherson Darren C. Tomlinson |
| author_sort | Katarzyna Z. Haza |
| collection | DOAJ |
| description | Oncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores. |
| first_indexed | 2024-12-21T09:38:00Z |
| format | Article |
| id | doaj.art-9fb0e318fb534431a1e30f0ac4d27ca1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-12-21T09:38:00Z |
| publishDate | 2021-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-9fb0e318fb534431a1e30f0ac4d27ca12022-12-21T19:08:34ZengNature PortfolioNature Communications2041-17232021-06-0112111510.1038/s41467-021-24316-0RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric siteKatarzyna Z. Haza0Heather L. Martin1Ajinkya Rao2Amy L. Turner3Sophie E. Saunders4Britta Petersen5Christian Tiede6Kevin Tipping7Anna A. Tang8Modupe Ajayi9Thomas Taylor10Maia Harvey11Keri M. Fishwick12Thomas L. Adams13Thembaninkosi G. Gaule14Chi H. Trinh15Matthew Johnson16Alexander L. Breeze17Thomas A. Edwards18Michael J. McPherson19Darren C. Tomlinson20School of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsAvacta Life SciencesSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology, Astbury Centre for Structural and Molecular Biology, University of LeedsOncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores.https://doi.org/10.1038/s41467-021-24316-0 |
| spellingShingle | Katarzyna Z. Haza Heather L. Martin Ajinkya Rao Amy L. Turner Sophie E. Saunders Britta Petersen Christian Tiede Kevin Tipping Anna A. Tang Modupe Ajayi Thomas Taylor Maia Harvey Keri M. Fishwick Thomas L. Adams Thembaninkosi G. Gaule Chi H. Trinh Matthew Johnson Alexander L. Breeze Thomas A. Edwards Michael J. McPherson Darren C. Tomlinson RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site Nature Communications |
| title | RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site |
| title_full | RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site |
| title_fullStr | RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site |
| title_full_unstemmed | RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site |
| title_short | RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site |
| title_sort | ras inhibiting biologics identify and probe druggable pockets including an sii α3 allosteric site |
| url | https://doi.org/10.1038/s41467-021-24316-0 |
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