7JME

Structure of the SARS-CoV-2 NSP3 Macro X domain in complex with cyclic AMP

7JME の概要

• エントリーDOI: 10.2210/pdb7jme/pdb
• 分子名称: Non-structural protein 3, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: macro domain, camp, cyclic amp, viral protein, sars-cov-2, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18823.31

構造登録者

Vuksanovic, N.,Melkonian, T.R.,Silvaggi, N.R. (登録日: 2020-07-31, 公開日: 2020-09-02, 最終更新日: 2023-10-18)

主引用文献

Virdi, R.S.,Bavisotto, R.V.,Hopper, N.C.,Vuksanovic, N.,Melkonian, T.R.,Silvaggi, N.R.,Frick, D.N.
Discovery of Drug-Like Ligands for the Mac1 Domain of SARS-CoV-2 Nsp3.
Slas Discov, 25:1162-1170, 2020

PubMed Abstract: Small molecules that bind the SARS-CoV-2 nonstructural protein 3 Mac1 domain in place of ADP-ribose could be useful as molecular probes or scaffolds for COVID-19 antiviral drug discovery because Mac1 has been linked to the ability of coronaviruses to evade cellular detection. A high-throughput assay based on differential scanning fluorimetry (DSF) was therefore optimized and used to identify possible Mac1 ligands in small libraries of drugs and drug-like compounds. Numerous promising compounds included nucleotides, steroids, β-lactams, and benzimidazoles. The main drawback to this approach was that a high percentage of compounds in some libraries were found to influence the observed Mac1 melting temperature. To prioritize DSF screening hits, the shapes of the observed melting curves and initial assay fluorescence were examined, and the results were compared with virtual screens performed using AutoDock Vina. The molecular basis for alternate ligand binding was also examined by determining a structure of one of the hits, cyclic adenosine monophosphate, with atomic resolution.

PubMed: 32981460
DOI: 10.1177/2472555220960428

実験手法

X-RAY DIFFRACTION (1.55 Å)