4UFX

Plasmodium vivax N-myristoyltransferase in complex with a pyridyl inhibitor (compound 19)

4UFX の概要

• エントリーDOI: 10.2210/pdb4ufx/pdb
• 関連するPDBエントリー: 4UFV 4UFW
• 分子名称: GLYCYLPEPTIDE N-TETRADECANOYLTRANSFERASE, N-[2-(3-methoxyphenyl)ethanimidoyl]-2-piperidin-4-yloxy-pyridine-3-carboxamide, 2-oxopentadecyl-CoA, ... (8 entities in total)
• 機能のキーワード: transferase, myristoylation, malaria, inhibitor, pyridyl
• 由来する生物種: PLASMODIUM VIVAX (MALARIA PARASITE P. VIVAX)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 140182.24

構造登録者

Yu, Z.,Brannigan, J.A.,Rangachari, K.,Heal, W.P.,Wilkinson, A.J.,Holder, A.A.,Tate, E.W.,Leatherbarrow, R.J. (登録日: 2015-03-19, 公開日: 2016-02-03, 最終更新日: 2024-05-08)

主引用文献

Yu, Z.,Brannigan, J.A.,Rangachari, K.,Heal, W.P.,Wilkinson, A.J.,Holder, A.A.,Leatherbarrow, R.J.,Tate, E.W.
Discovery of Pyridyl-Based Inhibitors of Plasmodium Falciparum N-Myristoyltransferase
Medchemcomm, 6:1767-, 2015

PubMed Abstract: -Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative , providing a versatile platform to study the effects of substitution on the scaffold, which yielded pyridyl . This molecule exhibited improved enzyme and cellular potency, and reduced lipophilicity compared to inhibitor . Further structure-based inhibitor design led to the discovery of , the most potent inhibitor in this series, which showed single-digit nM enzyme affinity and sub-μM anti-plasmodial activity.

PubMed: 26962430
DOI: 10.1039/C5MD00242G

実験手法

X-RAY DIFFRACTION (1.49 Å)