5RMJ

PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 helicase in complex with Z68299550

5RMJ の概要

• エントリーDOI: 10.2210/pdb5rmj/pdb
• Group deposition: PanDDA analysis group deposition (G_1002164)
• 分子名称: Helicase, 3-chloro-N-(1-hydroxy-2-methylpropan-2-yl)benzamide, ZINC ION, ... (5 entities in total)
• 機能のキーワード: sgc - diamond i04-1 fragment screening, pandda, xchemexplorer, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 134861.09

構造登録者

Newman, J.A.,Yosaatmadja, Y.,Douangamath, A.,Aimon, A.,Powell, A.J.,Dias, A.,Fearon, D.,Dunnett, L.,Brandao-Neto, J.,Krojer, T.,Skyner, R.,Gorrie-Stone, T.,Thompson, W.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.,Bountra, C.,Gileadi, O. (登録日: 2020-09-16, 公開日: 2020-09-30, 最終更新日: 2024-05-22)

主引用文献

Newman, J.A.,Douangamath, A.,Yadzani, S.,Yosaatmadja, Y.,Aimon, A.,Brandao-Neto, J.,Dunnett, L.,Gorrie-Stone, T.,Skyner, R.,Fearon, D.,Schapira, M.,von Delft, F.,Gileadi, O.
Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase.
Nat Commun, 12:4848-4848, 2021

PubMed Abstract: There is currently a lack of effective drugs to treat people infected with SARS-CoV-2, the cause of the global COVID-19 pandemic. The SARS-CoV-2 Non-structural protein 13 (NSP13) has been identified as a target for anti-virals due to its high sequence conservation and essential role in viral replication. Structural analysis reveals two "druggable" pockets on NSP13 that are among the most conserved sites in the entire SARS-CoV-2 proteome. Here we present crystal structures of SARS-CoV-2 NSP13 solved in the APO form and in the presence of both phosphate and a non-hydrolysable ATP analog. Comparisons of these structures reveal details of conformational changes that provide insights into the helicase mechanism and possible modes of inhibition. To identify starting points for drug development we have performed a crystallographic fragment screen against NSP13. The screen reveals 65 fragment hits across 52 datasets opening the way to structure guided development of novel antiviral agents.

PubMed: 34381037
DOI: 10.1038/s41467-021-25166-6

実験手法

X-RAY DIFFRACTION (2.1 Å)