4EHV

Human p38 MAP kinase in complex with NP-F10 and RL87

4EHV の概要

• エントリーDOI: 10.2210/pdb4ehv/pdb
• 関連するPDBエントリー: 4EH2 4EH3 4EH4 4EH5 4EH6
• 分子名称: Mitogen-activated protein kinase 14, (1R,5S)-3-(4-chlorobenzoyl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, N~4~-cyclopropyl-2-phenylquinazoline-4,7-diamine, ... (4 entities in total)
• 機能のキーワード: map kinase insert, kinase-ligand complex, np-fragment, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q16539
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42531.77

構造登録者

Over, B.,Gruetter, C.,Waldmann, H.,Rauh, D. (登録日: 2012-04-04, 公開日: 2012-12-05, 最終更新日: 2023-09-13)

主引用文献

Over, B.,Wetzel, S.,Grutter, C.,Nakai, Y.,Renner, S.,Rauh, D.,Waldmann, H.
Natural-product-derived fragments for fragment-based ligand discovery.
Nat Chem, 5:21-28, 2012

PubMed Abstract: Fragment-based ligand and drug discovery predominantly employs sp(2)-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp(3)-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38α MAP kinase and of inhibitors of several phosphatases.

PubMed: 23247173
DOI: 10.1038/nchem.1506

実験手法

X-RAY DIFFRACTION (1.6 Å)