Combining 'dry' co-crystallization and in situ diffraction to facilitate ligand screening by X-ray crystallography
| Autor: | Frédéric Allemand, Vanessa Delfosse, Michel Pirocchi, Jean Luc Ferrer, William Bourguet, Gilles Labesse, Muriel Gelin, Jean-François Guichou, François Hoh, Y. Sallaz-Damaz |
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| Přispěvatelé: | Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
In situ
Diffraction Crystallography X-Ray Ligands law.invention Cyclophilins Structural Biology law Drug Discovery Animals Humans Crystallization Mitogen-Activated Protein Kinase 1 [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Drug discovery Chemistry Ligand Proteins General Medicine Rats PPAR gamma Crystallography Beamline X-ray crystallography Muramidase Protein crystallization Chickens Cyclophilin D |
| Zdroj: | Acta Crystallographica Section D: Biological Crystallography Acta Crystallographica Section D: Biological Crystallography, International Union of Crystallography, 2015, 71 (Pt 8), pp.1777-87. ⟨10.1107/S1399004715010342⟩ Acta crystallographica Section D : Structural biology [1993-...] Acta crystallographica Section D : Structural biology [1993-..], 2015, 71 (Pt 8), pp.1777-87. ⟨10.1107/S1399004715010342⟩ |
| ISSN: | 0907-4449 2059-7983 |
| DOI: | 10.1107/S1399004715010342⟩ |
| Popis: | X-ray crystallography is an established technique for ligand screening in fragment-based drug-design projects, but the required manual handling steps – soaking crystals with ligand and the subsequent harvesting – are tedious and limit the throughput of the process. Here, an alternative approach is reported: crystallization plates are pre-coated with potential binders prior to protein crystallization and X-ray diffraction is performed directly `in situ' (or in-plate). Its performance is demonstrated on distinct and relevant therapeutic targets currently being studied for ligand screening by X-ray crystallography using either a bending-magnet beamline or a rotating-anode generator. The possibility of using DMSO stock solutions of the ligands to be coated opens up a route to screening most chemical libraries. |
| Databáze: | OpenAIRE |
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