5BUE

ERK2 complexed with N-benzylpyridone tetrahydroazaindazole

5BUE の概要

• エントリーDOI: 10.2210/pdb5bue/pdb
• 関連するPDBエントリー: 1ERK 5BUI 5BUJ
• 分子名称: Mitogen-activated protein kinase 1, 1-benzyl-4-[3-(pyridin-4-yl)-2,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]pyridin-2(1H)-one, NICKEL (II) ION, ... (4 entities in total)
• 機能のキーワード: erk kinase, atp inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytoskeleton, spindle : P28482
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41909.76

構造登録者

Bellamacina, C.R.,Shu, W.,Bussiere, D.E.,Bagdanoff, J.T. (登録日: 2015-06-03, 公開日: 2015-07-15, 最終更新日: 2024-03-06)

主引用文献

Bagdanoff, J.T.,Jain, R.,Han, W.,Poon, D.,Lee, P.S.,Bellamacina, C.,Lindvall, M.
Ligand efficient tetrahydro-pyrazolopyridines as inhibitors of ERK2 kinase.
Bioorg.Med.Chem.Lett., 25:3626-3629, 2015

PubMed Abstract: A series of structure based drug design hypotheses and focused screening efforts drove improvements in the potency and lipophilic efficiency of tetrahydro-pyrazolopyridine based ERK2 inhibitors. Elaboration of a fragment chemical lead established a new lipophilic aryl-Tyr interaction resulting in a substantial potency improvement. Subsequent cleavage of the lipophilic moiety led to reconfiguration of the ligand bound binding cleft. The reconfiguration established a polar contact between a newly liberated N-H and a vicinal Asp, resulting in further improvements in lipophilic efficiency and in vitro clearance.

PubMed: 26144345
DOI: 10.1016/j.bmcl.2015.06.063

実験手法

X-RAY DIFFRACTION (2.4 Å)