2ITK

human Pin1 bound to D-PEPTIDE

2ITK の概要

• エントリーDOI: 10.2210/pdb2itk/pdb
• 関連するPDBエントリー: 1F8A 1PIN 2ITI
• 分子名称: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, D-Peptide, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, ... (4 entities in total)
• 機能のキーワード: pin1, isomerase, ww domain, isomerase-isomerase inhibitor complex, isomerase/isomerase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 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: 19685.78

構造登録者

Noel, J.P.,Zhang, Y. (登録日: 2006-10-19, 公開日: 2007-05-22, 最終更新日: 2023-11-15)

主引用文献

Zhang, Y.,Daum, S.,Wildemann, D.,Zhou, X.Z.,Verdecia, M.A.,Bowman, M.E.,Lucke, C.,Hunter, T.,Lu, K.P.,Fischer, G.,Noel, J.P.
Structural basis for high-affinity peptide inhibition of human Pin1.
Acs Chem.Biol., 2:320-328, 2007

PubMed Abstract: Human Pin1 is a key regulator of cell-cycle progression and plays growth-promoting roles in human cancers. High-affinity inhibitors of Pin1 may provide a unique opportunity for disrupting oncogenic pathways. Here we report two high-resolution X-ray crystal structures of human Pin1 bound to non-natural peptide inhibitors. The structures of the bound high-affinity peptides identify a type-I beta-turn conformation for Pin1 prolyl peptide isomerase domain-peptide binding and an extensive molecular interface for high-affinity recognition. Moreover, these structures suggest chemical elements that may further improve the affinity and pharmacological properties of future peptide-based Pin inhibitors. Finally, an intramolecular hydrogen bond observed in both peptide complexes mimics the cyclic conformation of FK506 and rapamycin. Both FK506 and rapamycin are clinically important inhibitors of other peptidyl-prolyl cis-trans isomerases. This comparative discovery suggests that a cyclic peptide polyketide bridge, like that found in FK506 and rapamycin or a similar linkage, may significantly improve the binding affinity of structure-based Pin1 inhibitors.

PubMed: 17518432
DOI: 10.1021/cb7000044

実験手法

X-RAY DIFFRACTION (1.45 Å)