High-throughput structures of protein–ligand complexes at room temperature using serial femtosecond crystallography
| Autor: | Tadeo Moreno-Chicano, Ali Ebrahim, Danny Axford, Martin V. Appleby, John H. Beale, Amanda K. Chaplin, Helen M. E. Duyvesteyn, Reza A. Ghiladi, Shigeki Owada, Darren A. Sherrell, Richard W. Strange, Hiroshi Sugimoto, Kensuke Tono, Jonathan A. R. Worrall, Robin L. Owen, Michael A. Hough |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | IUCrJ, Vol 6, Iss 6, Pp 1074-1085 (2019) |
| Druh dokumentu: | article |
| ISSN: | 2052-2525 20522525 |
| DOI: | 10.1107/S2052252519011655 |
| Popis: | High-throughput X-ray crystal structures of protein–ligand complexes are critical to pharmaceutical drug development. However, cryocooling of crystals and X-ray radiation damage may distort the observed ligand binding. Serial femtosecond crystallography (SFX) using X-ray free-electron lasers (XFELs) can produce radiation-damage-free room-temperature structures. Ligand-binding studies using SFX have received only modest attention, partly owing to limited beamtime availability and the large quantity of sample that is required per structure determination. Here, a high-throughput approach to determine room-temperature damage-free structures with excellent sample and time efficiency is demonstrated, allowing complexes to be characterized rapidly and without prohibitive sample requirements. This yields high-quality difference density maps allowing unambiguous ligand placement. Crucially, it is demonstrated that ligands similar in size or smaller than those used in fragment-based drug design may be clearly identified in data sets obtained from |
| Databáze: | Directory of Open Access Journals |
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