3RLR

Co-crystal structure of the HSP90 ATP binding domain in complex with 4-(2,4-dichloro-5-methoxyphenyl)-2,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

3RLR の概要

• エントリーDOI: 10.2210/pdb3rlr/pdb
• 関連するPDBエントリー: 3RLP 3RLQ
• 分子名称: Heat shock protein HSP 90-alpha, 4-(2,4-dichloro-5-methoxyphenyl)-2,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: chaperone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07900
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51955.07

構造登録者

Kung, P.-P.,Sinnema, P.-J.,Richardson, P.,Hickey, M.J.,Gajiwala, K.S.,Wang, F.,Huang, B.,McClellan, G.,Wang, J.,Maegley, K.,Bergqvist, S.,Mehta, P.P.,Kania, R. (登録日: 2011-04-20, 公開日: 2011-06-08, 最終更新日: 2024-02-28)

主引用文献

Kung, P.P.,Sinnema, P.J.,Richardson, P.,Hickey, M.J.,Gajiwala, K.S.,Wang, F.,Huang, B.,McClellan, G.,Wang, J.,Maegley, K.,Bergqvist, S.,Mehta, P.P.,Kania, R.
Design strategies to target crystallographic waters applied to the Hsp90 molecular chaperone.
Bioorg.Med.Chem.Lett., 21:3557-3562, 2011

PubMed Abstract: A series of novel and potent small molecule Hsp90 inhibitors was optimized using X-ray crystal structures. These compounds bind in a deep pocket of the Hsp90 enzyme that is partially comprised by residues Asn51 and Ser52. Displacement of several water molecules observed crystallographically in this pocket using rule-based strategies led to significant improvements in inhibitor potency. An optimized inhibitor (compound 17) exhibited potent Hsp90 inhibition in ITC, biochemical, and cell-based assays (K(d)=1.3 nM, K(i)=15 nM, and cellular IC(50)=0.5 μM).

PubMed: 21612924
DOI: 10.1016/j.bmcl.2011.04.130

実験手法

X-RAY DIFFRACTION (1.7 Å)