7PLR
Crystal structure of the N-terminal endonuclease domain of La Crosse virus L-protein bound to compound Baloxavir
This is a non-PDB format compatible entry.
Summary for 7PLR
| Entry DOI | 10.2210/pdb7plr/pdb |
| Descriptor | RNA-directed RNA polymerase L, Baloxavir acid, FORMIC ACID, ... (6 entities in total) |
| Functional Keywords | complex, inhibitor, endonuclease, transferase |
| Biological source | Bunyavirus La Crosse |
| Total number of polymer chains | 4 |
| Total formula weight | 89166.46 |
| Authors | Feracci, M.,Hernandez, S.,Vincentelli, R.,Ferron, F.,Reguera, J.,Canard, B.,Alvarez, K. (deposition date: 2021-09-01, release date: 2022-09-14, Last modification date: 2024-09-18) |
| Primary citation | Feracci, M.,Hernandez, S.,Garlatti, L.,Mondielli, C.,Vincentelli, R.,Canard, B.,Reguera, J.,Ferron, F.,Alvarez, K. Biophysical and structural study of La Crosse virus endonuclease inhibition for the development of new antiviral options. Iucrj, 11:374-383, 2024 Cited by PubMed Abstract: The large Bunyavirales order includes several families of viruses with a segmented ambisense (-) RNA genome and a cytoplasmic life cycle that starts by synthesizing viral mRNA. The initiation of transcription, which is common to all members, relies on an endonuclease activity that is responsible for cap-snatching. In La Crosse virus, an orthobunyavirus, it has previously been shown that the cap-snatching endonuclease resides in the N-terminal domain of the L protein. Orthobunyaviruses are transmitted by arthropods and cause diseases in cattle. However, California encephalitis virus, La Crosse virus and Jamestown Canyon virus are North American species that can cause encephalitis in humans. No vaccines or antiviral drugs are available. In this study, three known Influenza virus endonuclease inhibitors (DPBA, L-742,001 and baloxavir) were repurposed on the La Crosse virus endonuclease. Their inhibition was evaluated by fluorescence resonance energy transfer and their mode of binding was then assessed by differential scanning fluorimetry and microscale thermophoresis. Finally, two crystallographic structures were obtained in complex with L-742,001 and baloxavir, providing access to the structural determinants of inhibition and offering key information for the further development of Bunyavirales endonuclease inhibitors. PubMed: 38656310DOI: 10.1107/S205225252400304X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.64 Å) |
Structure validation
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