2AMQ

Crystal Structure Of SARS_CoV Mpro in Complex with an Inhibitor N3

2AMQ の概要

• エントリーDOI: 10.2210/pdb2amq/pdb
• 関連するPDBエントリー: 1UJ1 2AMD 2AMP
• 関連するBIRD辞書のPRD_ID: PRD_002214
• 分子名称: 3C-like proteinase, N-[(5-METHYLISOXAZOL-3-YL)CARBONYL]ALANYL-L-VALYL-N~1~-((1R,2Z)-4-(BENZYLOXY)-4-OXO-1-{[(3R)-2-OXOPYRROLIDIN-3-YL]METHYL}BUT-2-ENYL)-L-LEUCINAMIDE (3 entities in total)
• 機能のキーワード: anti-parallel b-barrel, anti-parallel a-helices, hydrolase
• 由来する生物種: SARS coronavirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 69937.75

構造登録者

Yang, H.,Xue, X.,Yang, K.,Zhao, Q.,Bartlam, M.,Rao, Z. (登録日: 2005-08-10, 公開日: 2005-09-13, 最終更新日: 2024-10-30)

主引用文献

Yang, H.,Xie, W.,Xue, X.,Yang, K.,Ma, J.,Liang, W.,Zhao, Q.,Zhou, Z.,Pei, D.,Ziebuhr, J.,Hilgenfeld, R.,Yuen, K.Y.,Wong, L.,Gao, G.,Chen, S.,Chen, Z.,Ma, D.,Bartlam, M.,Rao, Z.
Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases.
Plos Biol., 3:324-334, 2005

PubMed Abstract: The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of Mpro-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.

PubMed: 16128623
DOI: 10.1371/journal.pbio.0030324

実験手法

X-RAY DIFFRACTION (2.3 Å)