Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL)
Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domai...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2018
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| _version_ | 1797077896618049536 |
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| author | Heidenreich, D Moustakim, M Schmidt, J Merk, D Brennan, P Fedorov, O Chaikuad, A Knapp, S |
| author_facet | Heidenreich, D Moustakim, M Schmidt, J Merk, D Brennan, P Fedorov, O Chaikuad, A Knapp, S |
| author_sort | Heidenreich, D |
| collection | OXFORD |
| description | Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family. |
| first_indexed | 2024-03-07T00:24:37Z |
| format | Journal article |
| id | oxford-uuid:7db781c0-59d7-4461-b41b-3173d6e1f226 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:24:37Z |
| publishDate | 2018 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:7db781c0-59d7-4461-b41b-3173d6e1f2262022-03-26T21:05:24ZStructure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL)Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7db781c0-59d7-4461-b41b-3173d6e1f226EnglishSymplectic Elements at OxfordAmerican Chemical Society2018Heidenreich, DMoustakim, MSchmidt, JMerk, DBrennan, PFedorov, OChaikuad, AKnapp, SLysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family. |
| spellingShingle | Heidenreich, D Moustakim, M Schmidt, J Merk, D Brennan, P Fedorov, O Chaikuad, A Knapp, S Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) |
| title | Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) |
| title_full | Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) |
| title_fullStr | Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) |
| title_full_unstemmed | Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) |
| title_short | Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) |
| title_sort | structure based approach toward identification of inhibitory fragments for eleven nineteen leukemia protein enl |
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