7BF5

Crystal structure of SARS-CoV-2 macrodomain in complex with ADP-ribose-phosphate (ADP-ribose-2'-phosphate, ADPRP)

7BF5 の概要

• エントリーDOI: 10.2210/pdb7bf5/pdb
• 分子名称: NSP3 macrodomain, MAGNESIUM ION, [(2R,3R,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-3-HYDROXY-4-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL [(2R,3S,4R,5R)-3,4,5-TRIHYDROXYTETRAHYDROFURAN-2-YL]METHYL DIHYDROGEN DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: nsp3, macrodomain, sars-cov-2, adp-ribose-phosphate, adprp, covid-19, structural genomics, structural genomics consortium, sgc, 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: 5
• 化学式量合計: 96694.71

構造登録者

Ni, X.,Knapp, S.,Chaikuad, A.,Structural Genomics Consortium (SGC) (登録日: 2020-12-31, 公開日: 2021-01-13, 最終更新日: 2025-10-15)

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 (2.05 Å)