4J5C

Human Cyclophilin D Complexed with an Inhibitor

4J5C の概要

• エントリーDOI: 10.2210/pdb4j5c/pdb
• 関連するPDBエントリー: 4J58 4J59 4J5A 4J5B 4J5D 4J5E
• 分子名称: Peptidyl-prolyl cis-trans isomerase F, mitochondrial, 1-(4-aminobenzyl)-3-[(2S)-4-(methylsulfanyl)-1-{(2R)-2-[2-(methylsulfanyl)phenyl]pyrrolidin-1-yl}-1-oxobutan-2-yl]urea (3 entities in total)
• 機能のキーワード: isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix : P30405
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18124.79

構造登録者

Gelin, M.,Colliandre, L.,Bessin, Y.,Guichou, J.F. (登録日: 2013-02-08, 公開日: 2014-02-19, 最終更新日: 2024-02-28)

主引用文献

Ahmed-Belkacem, A.,Colliandre, L.,Ahnou, N.,Nevers, Q.,Gelin, M.,Bessin, Y.,Brillet, R.,Cala, O.,Douguet, D.,Bourguet, W.,Krimm, I.,Pawlotsky, J.M.,Guichou, J.F.
Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities.
Nat Commun, 7:12777-12777, 2016

PubMed Abstract: Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug-drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.

PubMed: 27652979
DOI: 10.1038/ncomms12777

実験手法

X-RAY DIFFRACTION (1.03 Å)