Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions
Small molecule stabilizers of protein–protein interactions hold great therapeutic potential. Based on virtual screening and molecular docking, the authors here develop a strategy to evolve weak, promiscuous inhibitors of 14-3-3 interactions into selective stabilizers of the 14-3-3/ChREBP complex.
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2020-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-020-17741-0 |
| id |
doaj-8ff8fc48608f42e5b0be3c2e5c15b283 |
|---|---|
| record_format |
Article |
| spelling |
doaj-8ff8fc48608f42e5b0be3c2e5c15b2832021-08-08T11:38:22ZengNature Publishing GroupNature Communications2041-17232020-08-011111910.1038/s41467-020-17741-0Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactionsEline Sijbesma0Emira Visser1Kathrin Plitzko2Philipp Thiel3Lech-Gustav Milroy4Markus Kaiser5Luc Brunsveld6Christian Ottmann7Laboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of TechnologyLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of TechnologyChemical Biology, Center of Medical Biotechnology, Faculty of Biology, University of Duisburg-EssenInstitute for Biomedical Informatics and Medical Informatics, University of TübingenLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of TechnologyChemical Biology, Center of Medical Biotechnology, Faculty of Biology, University of Duisburg-EssenLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of TechnologyLaboratory of Chemical Biology and Institute for Complex Molecular Systems (ICMS), Department of Biomedical Engineering, Eindhoven University of TechnologySmall molecule stabilizers of protein–protein interactions hold great therapeutic potential. Based on virtual screening and molecular docking, the authors here develop a strategy to evolve weak, promiscuous inhibitors of 14-3-3 interactions into selective stabilizers of the 14-3-3/ChREBP complex.https://doi.org/10.1038/s41467-020-17741-0 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Eline Sijbesma Emira Visser Kathrin Plitzko Philipp Thiel Lech-Gustav Milroy Markus Kaiser Luc Brunsveld Christian Ottmann |
| spellingShingle |
Eline Sijbesma Emira Visser Kathrin Plitzko Philipp Thiel Lech-Gustav Milroy Markus Kaiser Luc Brunsveld Christian Ottmann Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions Nature Communications |
| author_facet |
Eline Sijbesma Emira Visser Kathrin Plitzko Philipp Thiel Lech-Gustav Milroy Markus Kaiser Luc Brunsveld Christian Ottmann |
| author_sort |
Eline Sijbesma |
| title |
Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions |
| title_short |
Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions |
| title_full |
Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions |
| title_fullStr |
Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions |
| title_full_unstemmed |
Structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions |
| title_sort |
structure-based evolution of a promiscuous inhibitor to a selective stabilizer of protein–protein interactions |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2020-08-01 |
| description |
Small molecule stabilizers of protein–protein interactions hold great therapeutic potential. Based on virtual screening and molecular docking, the authors here develop a strategy to evolve weak, promiscuous inhibitors of 14-3-3 interactions into selective stabilizers of the 14-3-3/ChREBP complex. |
| url |
https://doi.org/10.1038/s41467-020-17741-0 |
| work_keys_str_mv |
AT elinesijbesma structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT emiravisser structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT kathrinplitzko structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT philippthiel structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT lechgustavmilroy structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT markuskaiser structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT lucbrunsveld structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions AT christianottmann structurebasedevolutionofapromiscuousinhibitortoaselectivestabilizerofproteinproteininteractions |
| _version_ |
1721215750068240384 |