4MJV

Influenza Neuraminidase in complex with a novel antiviral compound

4MJV の概要

• エントリーDOI: 10.2210/pdb4mjv/pdb
• 関連するPDBエントリー: 4MJU
• 分子名称: Neuraminidase, (2E,5S,9R,10S)-10-(acetylamino)-2-imino-4-oxo-9-(pentan-3-yloxy)-1-thia-3-azaspiro[4.5]dec-6-ene-7-carboxylic acid, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: neuraminidase, sialidase, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion membrane : Q07599
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43592.08

構造登録者

Kerry, P.S. (登録日: 2013-09-04, 公開日: 2014-01-15, 最終更新日: 2024-11-20)

主引用文献

Mohan, S.,Kerry, P.S.,Bance, N.,Niikura, M.,Pinto, B.M.
Serendipitous discovery of a potent influenza virus a neuraminidase inhibitor.
Angew.Chem.Int.Ed.Engl., 53:1076-1080, 2014

PubMed Abstract: We have previously reported a potent neuraminidase inhibitor that comprises a carbocyclic analogue of zanamivir in which the hydrophilic glycerol side chain is replaced by the hydrophobic 3-pentyloxy group of oseltamivir. This hybrid inhibitor showed excellent inhibitory properties in the neuraminidase inhibition assay (Ki =0.46 nM; Ki (zanamivir) =0.16 nM) and in the viral replication inhibition assay in cell culture at 10(-8)  M. As part of this lead optimization, we now report a novel spirolactam that shows comparable inhibitory activity in the cell culture assay to that of our lead compound at 10(-7)  M. The compound was discovered serendipitously during the attempted synthesis of the isothiourea derivative of the original candidate. The X-ray crystal structure of the spirolactam in complex with the N8 subtype neuraminidase offers insight into the mode of inhibition.

PubMed: 24339250
DOI: 10.1002/anie.201308142

実験手法

X-RAY DIFFRACTION (2.65 Å)