6S5V

Crystal structure of the Cap-Midlink region of the H5N1 Influenza A virus polymerase in complex with a Cap-domain binding analogue

これはPDB形式変換不可エントリーです。

6S5V の概要

• エントリーDOI: 10.2210/pdb6s5v/pdb
• 分子名称: Polymerase basic protein 2, (1~{S},2~{S},3~{S},6~{R})-2-[[2-[5,7-bis(fluoranyl)-1~{H}-indol-3-yl]-5-fluoranyl-pyrimidin-4-yl]amino]-3,6-dimethyl-cyclohexane-1-carboxylic acid, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: influenza a, h5n1, influenza polymerase, cap binding analogue, viral protein
• 由来する生物種: Influenza A virus (A/duck/Fujian/13/2002(H5N1))
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70068.95

構造登録者

Keown, J.R.,Fodor, E.,Grimes, J.M. (登録日: 2019-07-02, 公開日: 2019-11-06, 最終更新日: 2024-05-15)

主引用文献

McGowan, D.C.,Balemans, W.,Embrechts, W.,Motte, M.,Keown, J.R.,Buyck, C.,Corbera, J.,Funes, M.,Moreno, L.,Cooymans, L.,Tahri, A.,Eymard, J.,Stoops, B.,Strijbos, R.,Van den Berg, J.,Fodor, E.,Grimes, J.M.,Koul, A.,Jonckers, T.H.M.,Raboisson, P.,Guillemont, J.
Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region.
J.Med.Chem., 62:9680-9690, 2019

PubMed Abstract: In the search for novel influenza inhibitors we evaluated 7-fluoro-substituted indoles as bioisosteric replacements for the 7-azaindole scaffold of Pimodivir, a PB2 (polymerase basic protein 2) inhibitor currently in clinical development. Specifically, a 5,7-difluoroindole derivative was identified as a potent and metabolically stable influenza inhibitor. demonstrated a favorable oral pharmacokinetic profile and in vivo efficacy in mice. In addition, it was found that was not at risk of metabolism via aldehyde oxidase, an advantage over previously described inhibitors of this class. The crystal structure of bound to influenza A PB2 cap region is disclosed here and deposited to the PDB.

PubMed: 31647875
DOI: 10.1021/acs.jmedchem.9b01091

実験手法

X-RAY DIFFRACTION (1.35 Å)