7PLR

Crystal structure of the N-terminal endonuclease domain of La Crosse virus L-protein bound to compound Baloxavir

これはPDB形式変換不可エントリーです。

7PLR の概要

• エントリーDOI: 10.2210/pdb7plr/pdb
• 分子名称: RNA-directed RNA polymerase L, Baloxavir acid, FORMIC ACID, ... (6 entities in total)
• 機能のキーワード: complex, inhibitor, endonuclease, transferase
• 由来する生物種: Bunyavirus La Crosse
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89166.46

構造登録者

Feracci, M.,Hernandez, S.,Vincentelli, R.,Ferron, F.,Reguera, J.,Canard, B.,Alvarez, K. (登録日: 2021-09-01, 公開日: 2022-09-14, 最終更新日: 2024-11-20)

主引用文献

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

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: 38656310
DOI: 10.1107/S205225252400304X

実験手法

X-RAY DIFFRACTION (2.64 Å)