8ULD

SARA CoV-2 3C-like protease in complex with GSK3487016A

8ULD の概要

• エントリーDOI: 10.2210/pdb8uld/pdb
• 分子名称: Replicase polyprotein 1a, N-[(benzyloxy)carbonyl]-4-fluoro-L-phenylalanyl-N-{(2S,3R)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]-4-[(propan-2-yl)amino]butan-2-yl}-L-leucinamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: sars cov-2, protease, inhibitor, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36914.94

構造登録者

Williams, S.P.,Concha, N.O. (登録日: 2023-10-16, 公開日: 2024-02-14, 最終更新日: 2024-10-30)

主引用文献

Barton, L.S.,Callahan, J.F.,Cantizani, J.,Concha, N.O.,Cotillo Torrejon, I.,Goodwin, N.C.,Joshi-Pangu, A.,Kiesow, T.J.,McAtee, J.J.,Mellinger, M.,Nixon, C.J.,Padron-Barthe, L.,Patterson, J.R.,Pearson, N.D.,Pouliot, J.J.,Rendina, A.R.,Buitrago Santanilla, A.,Schneck, J.L.,Sanz, O.,Thalji, R.K.,Ward, P.,Williams, S.P.,King, B.W.
Exploration of the P1 residue in 3CL protease inhibitors leading to the discovery of a 2-tetrahydrofuran P1 replacement.
Bioorg.Med.Chem., 100:117618-117618, 2024

PubMed Abstract: The virally encoded 3C-like protease (3CL) is a well-validated drug target for the inhibition of coronaviruses including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Most inhibitors of 3CL are peptidomimetic, with a γ-lactam in place of Gln at the P1 position of the pseudopeptide chain. An effort was pursued to identify a viable alternative to the γ-lactam P1 mimetic which would improve physicochemical properties while retaining affinity for the target. Discovery of a 2-tetrahydrofuran as a suitable P1 replacement that is a potent enzymatic inhibitor of 3CL in SARS-CoV-2 virus is described herein.

PubMed: 38309201
DOI: 10.1016/j.bmc.2024.117618

実験手法

X-RAY DIFFRACTION (1.8 Å)