9BF8

SARS-CoV-2 Papain-like Protease (PLpro) Untagged Crystal Structure

9BF8 の概要

• エントリーDOI: 10.2210/pdb9bf8/pdb
• 分子名称: ORF1a polyprotein, ZINC ION, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: protease, sars-cov-2, plpro, papain-like protease, coronavirus., 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: 1
• 化学式量合計: 35893.95

構造登録者

Al-Homoudi, A.I.,Engel, J.,Brunzelle, J.S.,Gavande, N.,Kovari, L.C. (登録日: 2024-04-17, 公開日: 2025-05-07)

主引用文献

Al-Homoudi, A.I.,Engel, J.,Muczynski, M.D.,Brunzelle, J.S.,Gavande, N.S.,Kovari, L.C.
Human Structural Homologues of SARS-CoV-2 PL pro as Anti-Targets: A Strategic Panel Analysis.
MicroPubl Biol, 2025:-, 2025

PubMed Abstract: COVID-19 is caused by SARS-CoV-2, a highly transmissible and pathogenic RNA betacoronavirus. Developing small-molecule antiviral inhibitors of the SARS-CoV-2 papain-like protease (PL ) is advantageous due to the enzyme's role in processing viral polyproteins and disrupting host immune sensing. Given the structural and functional similarities between PL and human deubiquitinases (DUBs), small-molecule inhibitors are frequently counter-screened for off-target activity using a panel of human DUBs. Through X-ray crystallography, DALI structural comparisons, and analysis, a high-quality crystal structure of SARS-CoV-2 PL enabled the identification of the closest structural human homologues of PL . Among the 27 human DUBs identified, USP46 and USP12 displayed the greatest structural similarity to PL , with alignment scores below 0.45 and RMSD values of 3.0 Å or less. Additionally, binding sites on ubiquitin-specific protease (USP46) and USP12, ancillary to the active site residues, share high sequence identity to the PL substrate binding sites that are often engaged by the most potent PL inhibitors. These findings offer a strong basis for choosing anti-targets and serve as a foundation for designing selective small-molecule PL inhibitors.

PubMed: 40297819
DOI: 10.17912/micropub.biology.001418

実験手法

X-RAY DIFFRACTION (1.85 Å)