2ZU5

complex structure of SARS-CoV 3CL protease with TG-0205486

2ZU5 の概要

• エントリーDOI: 10.2210/pdb2zu5/pdb
• 関連するPDBエントリー: 2ZTX 2ZTY 2ZTZ 2ZU1 2ZU2 2ZU3 2ZU4
• 関連するBIRD辞書のPRD_ID: PRD_000569
• 分子名称: 3C-like proteinase, N-[(benzyloxy)carbonyl]-O-tert-butyl-L-threonyl-N-[(1R)-4-cyclopropyl-4-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}butyl]-L-leucinamide (3 entities in total)
• 機能のキーワード: protease-inhibitor complex, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: SARS coronavirus (SARS-CoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34505.44

構造登録者

Hsu, M.F.,Lee, C.C.,Wang, A.H.-J. (登録日: 2008-10-12, 公開日: 2009-01-13, 最終更新日: 2024-11-20)

主引用文献

Lee, C.C.,Kuo, C.J.,Ko, T.P.,Hsu, M.F.,Tsui, Y.C.,Chang, S.C.,Yang, S.,Chen, S.J.,Chen, H.C.,Hsu, M.C.,Shih, S.R.,Liang, P.H.,Wang, A.H.-J.
Structural Basis of Inhibition Specificities of 3C and 3C-like Proteases by Zinc-coordinating and Peptidomimetic Compounds
J.Biol.Chem., 284:7646-7655, 2009

PubMed Abstract: Human coxsackievirus (CV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. In picornavirus, a chymotrypsin-like protease (3C(pro)) is required for viral replication by processing the polyproteins, and thus it is regarded as an antiviral drug target. A 3C-like protease (3CL(pro)) also exists in human coronaviruses (CoV) such as 229E and the one causing severe acute respiratory syndrome (SARS). To combat SARS, we previously had developed peptidomimetic and zinc-coordinating inhibitors of 3CL(pro). As shown in the present study, some of these compounds were also found to be active against 3C(pro) of CV strain B3 (CVB3). Several crystal structures of 3C(pro) from CVB3 and 3CL(pro) from CoV-229E and SARS-CoV in complex with the inhibitors were solved. The zinc-coordinating inhibitor is tetrahedrally coordinated to the His(40)-Cys(147) catalytic dyad of CVB3 3C(pro). The presence of specific binding pockets for the residues of peptidomimetic inhibitors explains the binding specificity. Our results provide a structural basis for inhibitor optimization and development of potential drugs for antiviral therapies.

PubMed: 19144641
DOI: 10.1074/jbc.M807947200

実験手法

X-RAY DIFFRACTION (1.65 Å)