7BF6

Crystal structure of SARS-CoV-2 macrodomain in complex with remdesivir metabolite GS-441524

7BF6 の概要

• エントリーDOI: 10.2210/pdb7bf6/pdb
• 分子名称: Papain-like protease nsp3, (2~{R},3~{R},4~{S},5~{R})-2-(4-azanylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolane-2-carbonitrile, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: nsp3, macrodomain, sars-cov-2, remdesivir, gs-441524, covid-19, structural genomics, structural genomics consortium, sgc, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 57213.25

構造登録者

Ni, X.,Knapp, S.,Chaikuad, A.,Structural Genomics Consortium,Structural Genomics Consortium (SGC) (登録日: 2020-12-31, 公開日: 2021-01-13, 最終更新日: 2024-01-31)

主引用文献

Ni, X.,Schroder, M.,Olieric, V.,Sharpe, M.E.,Hernandez-Olmos, V.,Proschak, E.,Merk, D.,Knapp, S.,Chaikuad, A.
Structural Insights into Plasticity and Discovery of Remdesivir Metabolite GS-441524 Binding in SARS-CoV-2 Macrodomain.
Acs Med.Chem.Lett., 12:603-609, 2021

PubMed Abstract: The nsP3 macrodomain is a conserved protein interaction module that plays essential regulatory roles in the host immune response by recognizing and removing posttranslational ADP-ribosylation sites during SARS-CoV-2 infection. Thus targeting this protein domain may offer a therapeutic strategy to combat current and future virus pandemics. To assist inhibitor development efforts, we report here a comprehensive set of macrodomain crystal structures complexed with diverse naturally occurring nucleotides, small molecules, and nucleotide analogues including GS-441524 and its phosphorylated analogue, active metabolites of remdesivir. The presented data strengthen our understanding of the SARS-CoV-2 macrodomain structural plasticity and provide chemical starting points for future inhibitor development.

PubMed: 33850605
DOI: 10.1021/acsmedchemlett.0c00684

実験手法

X-RAY DIFFRACTION (2.15 Å)