4I7B

Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR

4I7B の概要

• エントリーDOI: 10.2210/pdb4i7b/pdb
• 関連するPDBエントリー: 1K2F 2A25 2AN6 4I7C 4I7D
• 関連するBIRD辞書のPRD_ID: PRD_000939
• 分子名称: E3 ubiquitin-protein ligase SIAH1, Protein phyllopod, ZINC ION, ... (4 entities in total)
• 機能のキーワード: sina, beta sandwich, zinc finger, ubiquitin ligase, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q8IUQ4; Nucleus: Q27934
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 47347.82

構造登録者

Santelli, E.,Stebbins, J.L.,Feng, Y.,De, S.K.,Purves, A.,Motamedchaboki, K.,Wu, B.,Ronai, Z.A.,Liddington, R.C.,Pellecchia, M. (登録日: 2012-11-30, 公開日: 2013-08-14, 最終更新日: 2023-12-06)

主引用文献

Stebbins, J.L.,Santelli, E.,Feng, Y.,De, S.K.,Purves, A.,Motamedchaboki, K.,Wu, B.,Ronai, Z.A.,Liddington, R.C.,Pellecchia, M.
Structure-based design of covalent siah inhibitors.
Chem.Biol., 20:973-982, 2013

PubMed Abstract: The E3 ubiquitin ligase Siah regulates key cellular events that are central to cancer development and progression. A promising route to Siah inhibition is disrupting its interactions with adaptor proteins. However, typical of protein-protein interactions, traditional unbiased approaches to ligand discovery did not produce viable hits against this target, despite considerable effort and a multitude of approaches. Ultimately, a rational structure-based design strategy was successful for the identification of Siah inhibitors in which peptide binding drives specific covalent bond formation with the target. X-ray crystallography, mass spectrometry, and functional data demonstrate that these peptide mimetics are efficient covalent inhibitors of Siah and antagonize Siah-dependent regulation of Erk and Hif signaling in the cell. The proposed strategy may result useful as a general approach to the design of peptide-based inhibitors of other protein-protein interactions.

PubMed: 23891150
DOI: 10.1016/j.chembiol.2013.06.008

実験手法

X-RAY DIFFRACTION (3 Å)