3JYJ

Structure-Based Design of Novel PIN1 Inhibitors (II)

3JYJ の概要

• エントリーDOI: 10.2210/pdb3jyj/pdb
• 関連するPDBエントリー: 3I6C 3IK8 3IKD 3IKG
• 分子名称: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, (2R,4E)-2-[(naphthalen-2-ylcarbonyl)amino]-5-phenylpent-4-enoic acid (3 entities in total)
• 機能のキーワード: sbdd, small molecule, ppiase, cell cycle, isomerase, nucleus, phosphoprotein, rotamase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q13526
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28015.18

構造登録者

Greasley, S.E.,Ferre, R.A. (登録日: 2009-09-21, 公開日: 2010-04-07, 最終更新日: 2024-04-03)

主引用文献

Dong, L.,Marakovits, J.,Hou, X.,Guo, C.,Greasley, S.,Dagostino, E.,Ferre, R.,Johnson, M.C.,Kraynov, E.,Thomson, J.,Pathak, V.,Murray, B.W.
Structure-based design of novel human Pin1 inhibitors (II).
Bioorg.Med.Chem.Lett., 20:2210-2214, 2010

PubMed Abstract: Following the discovery of a novel series of phosphate-containing small molecular Pin1 inhibitors, the drug design strategy shifted to replacement of the phosphate group with an isostere with potential better pharmaceutical properties. The initial loss in potency of carboxylate analogs was likely due to weaker charge-charge interactions in the putative phosphate binding pocket and was subsequently recovered by structure-based optimization of ligand-protein interactions in the proline binding site, leading to the discovery of a sub-micromolar non-phosphate small molecular Pin1 inhibitor.

PubMed: 20207139
DOI: 10.1016/j.bmcl.2010.02.033

実験手法

X-RAY DIFFRACTION (1.87 Å)