Hitting a moving target: simulation and crystallography study of ATAD2 bromodomain blockers
Title | Hitting a moving target: simulation and crystallography study of ATAD2 bromodomain blockers |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Dolbois A., Batiste L., Wiedmer L., Dong J., Brütsch M., Huang D., Deerain N., Spiliotopoulos D., Cheng-Sánchez I., Laul E., Nevado C., Śledź P., Caflisch A. |
Journal | ACS Medicinal Chemistry Letters |
Volume | 11 |
Issue | 8 |
Pagination | 1573-1580 |
Date Published | 2020 Aug 13 |
Type of Article | Research Article |
Abstract | Small molecule ligand binding to the ATAD2 bromodomain is investigated here through the synergistic combination of molecular dynamics and protein crystallography. A previously unexplored conformation of the binding pocket upon rearrangement of the gatekeeper residue Ile1074 has been found. Further, our investigations reveal how minor structural differences in the ligands result in binding with different plasticity of the ZA loop for this difficult-to-drug bromodomain. |
DOI | 10.1021/acsmedchemlett.0c00080 |
pubindex | 0257 |
Alternate Journal | ACS Med. Chem. Lett. |
PubMed ID | 32832026 |
PubMed Central ID | PMC7429973 |
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