6YWK

Crystal structure of SARS-CoV-2 (Covid-19) NSP3 macrodomain in complex with HEPES

Summary for 6YWK

• Entry DOI: 10.2210/pdb6ywk/pdb
• Descriptor: NSP3 macrodomain, 1,2-ETHANEDIOL, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: nsp3, macrodomain, adp-ribose-1"-phosphatase, adrp, covid-19, sars-cov-2, structural genomics, structural genomics consortium, sgc, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 5
• Total formula weight: 95510.89

Authors

Ni, X.,Schroeder, M.,Olieric, V.,Sharpe, E.M.,Wojdyla, J.A.,Wang, M.,Knapp, S.,Chaikuad, A.,Structural Genomics Consortium (SGC) (deposition date: 2020-04-29, release date: 2020-05-06, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)