2QIQ

Structure-based Design and Synthesis and Biological Evaluation of Peptidomimetic SARS-3CLpro Inhibitors

2QIQ の概要

• エントリーDOI: 10.2210/pdb2qiq/pdb
• 関連するPDBエントリー: 2ALV
• 分子名称: Replicase polyprotein 1ab, ETHYL (4R)-4-{[(2R,5S)-5-{[N-(TERT-BUTOXYCARBONYL)-L-SERYL]AMINO}-6-METHYL-2-(3-METHYLBUT-2-EN-1-YL)-4-OXOHEPTANOYL]AMINO}-5-[(3R)-2-OXOPYRROLIDIN-3-YL]PENTANOATE (3 entities in total)
• 機能のキーワード: hydrolase, viral protein
• 由来する生物種: SARS coronavirus
• 細胞内の位置: Non-structural protein 3: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 4: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 6: Host membrane; Multi-pass membrane protein (Potential). Non-structural protein 7: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 8: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 9: Host cytoplasm, host perinuclear region (By similarity). Non-structural protein 10: Host cytoplasm, host perinuclear region (By similarity). Helicase: Host endoplasmic reticulum-Golgi intermediate compartment (Potential). Uridylate-specific endoribonuclease: Host cytoplasm, host perinuclear region (By similarity): P59641
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33966.85

構造登録者

Grum-Tokars, V. (登録日: 2007-07-05, 公開日: 2008-02-12, 最終更新日: 2023-08-30)

主引用文献

Ghosh, A.K.,Xi, K.,Grum-Tokars, V.,Xu, X.,Ratia, K.,Fu, W.,Houser, K.V.,Baker, S.C.,Johnson, M.E.,Mesecar, A.D.
Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors.
Bioorg.Med.Chem.Lett., 17:5876-5880, 2007

PubMed Abstract: Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P(4)-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.

PubMed: 17855091
DOI: 10.1016/j.bmcl.2007.08.031

実験手法

X-RAY DIFFRACTION (1.9 Å)