High-throughput structures of protein–ligand complexes at room temperature using serial femtosecond crystallography
書誌事項
- 公開日
- 2019-10-10
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by/4.0/legalcode
- http://creativecommons.org/licenses/by/4.0/legalcode
- DOI
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- 10.1107/s2052252519011655
- 公開者
- International Union of Crystallography (IUCr)
説明
<jats:p>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 <1000 diffraction images. This efficiency in both sample and XFEL beamtime opens the door to true high-throughput screening of protein–ligand complexes using SFX.</jats:p>
収録刊行物
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- IUCrJ
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IUCrJ 6 (6), 1074-1085, 2019-10-10
International Union of Crystallography (IUCr)
