Identifying ligand-binding hot spots in proteins using brominated fragments
| Autor: | J. Preben Morth, Morten K. Grøftehauge, Poul Nissen, Troels Skrydstrup, M. Therkelsen, Rolf H. Taaning |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Halogenation
Biophysics Gene Expression Plasma protein binding Peptide Elongation Factor Tu Crystallography X-Ray Ligands Peptide Mapping Peptides Cyclic Biochemistry Molecular Docking Simulation Mass Spectrometry Protein Structure Secondary Small Molecule Libraries Bacterial Proteins RNA Transfer Structural Biology Escherichia coli Genetics Binding site Binding Sites biology Thermus thermophilus Laboratory Communications Resolution (electron density) food and beverages Condensed Matter Physics biology.organism_classification Small molecule Recombinant Proteins Thiazoles Crystallography Transfer RNA Guanosine Triphosphate Protein Binding |
| Zdroj: | Grøftehauge, M K, Therkelsen, M O, Taaning, R, Skrydstrup, T, Morth, J P & Nissen, P 2013, ' Identifying ligand-binding hot spots in proteins using brominated fragments ', Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online, vol. 69, no. Pt 9, pp. 1060-1065 . https://doi.org/10.1107/S1744309113018551 |
| DOI: | 10.1107/S1744309113018551 |
| Popis: | High-quality crystals of Thermus thermophilus EF-Tu in the GTP-bound conformation at 1.7-2.7 Å resolution were used to test 18 small organic molecules, all brominated for confident identification in the anomalous difference maps. From this relatively small collection, it was possible to identify a small molecule bound in the functionally important tRNA CCA-end binding pocket. The antibiotic GE2270 A is known to interact with the same pocket in EF-Tu and to disrupt the association with tRNA. Bromide could be located from peaks in the anomalous map in data truncated to very low resolution without refining the structure. Considering the speed with which diffraction data can be collected today, it is proposed that it is worthwhile to collect the extra data from fragment screens while crystals are at hand to increase the knowledge of biological function and drug binding in an experimental structural context. |
| Databáze: | OpenAIRE |
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