6XZV

Structure of zVDR LBD-Calcitriol in complex with chimera 18

6XZV の概要

• エントリーDOI: 10.2210/pdb6xzv/pdb
• 分子名称: Vitamin D3 receptor A, URA-UIA-URL-URY-URV-UZN-LYS, 5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, foldamer, helix mimicry, protein-protein interaction, gene regulation
• 由来する生物種: Danio rerio (Zebrafish); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35429.53

構造登録者

Buratto, J.,Belorusova, A.Y.,Rochel, N.,Guichard, G. (登録日: 2020-02-05, 公開日: 2021-02-17, 最終更新日: 2024-01-24)

主引用文献

Cussol, L.,Mauran-Ambrosino, L.,Buratto, J.,Belorusova, A.Y.,Neuville, M.,Osz, J.,Fribourg, S.,Fremaux, J.,Dolain, C.,Goudreau, S.R.,Rochel, N.,Guichard, G.
Structural Basis for alpha-Helix Mimicry and Inhibition of Protein-Protein Interactions with Oligourea Foldamers.
Angew.Chem.Int.Ed.Engl., 60:2296-2303, 2021

PubMed Abstract: Efficient optimization of a peptide lead into a drug candidate frequently needs further transformation to augment properties such as bioavailability. Among the different options, foldamers, which are sequence-based oligomers with precise folded conformation, have emerged as a promising technology. We introduce oligourea foldamers to reduce the peptide character of inhibitors of protein-protein interactions (PPI). However, the precise design of such mimics is currently limited by the lack of structural information on how these foldamers adapt to protein surfaces. We report a collection of X-ray structures of peptide-oligourea hybrids in complex with ubiquitin ligase MDM2 and vitamin D receptor and show how such hybrid oligomers can be designed to bind with high affinity to protein targets. This work should enable the generation of more effective foldamer-based disruptors of PPIs in the context of peptide lead optimization.

PubMed: 32935897
DOI: 10.1002/anie.202008992

実験手法

X-RAY DIFFRACTION (2.3 Å)