4I80

Crystal structure of human menin in complex with a high-affinity macrocyclic peptidomimetics

4I80 の概要

• エントリーDOI: 10.2210/pdb4i80/pdb
• 関連するPDBエントリー: 3U84 3U85 3U88
• 関連するBIRD辞書のPRD_ID: PRD_000967
• 分子名称: Menin, macrocyclic peptidomimetic (2 entities in total)
• 機能のキーワード: menin, men1, mll, macrocyclic peptidomimetic, transcription, transcription-inhibitor complex, transcription/inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : O00255
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62188.62

構造登録者

Huang, J.,Lei, M. (登録日: 2012-12-01, 公開日: 2013-03-06, 最終更新日: 2024-10-30)

主引用文献

Zhou, H.,Liu, L.,Huang, J.,Bernard, D.,Karatas, H.,Navarro, A.,Lei, M.,Wang, S.
Structure-Based Design of High-Affinity Macrocyclic Peptidomimetics to Block the Menin-Mixed Lineage Leukemia 1 (MLL1) Protein-Protein Interaction.
J.Med.Chem., 56:1113-1123, 2013

PubMed Abstract: Menin is an essential oncogenic cofactor for mixed lineage leukemia 1 (MLL1)-mediated leukemogenesis through its direct interaction with MLL1. Targeting the menin-MLL1 protein-protein interaction represents a promising strategy to block MLL1-mediated leukemogenesis. Employing a structure-based approach and starting from a linear MLL1 octapeptide, we have designed a class of potent macrocyclic peptidomimetic inhibitors of the menin-MLL1 interaction. The most potent macrocyclic peptidomimetic (MCP-1), 34, binds to menin with a K(i) value of 4.7 nM and is >600 times more potent than the corresponding acyclic peptide. Compound 34 is also less peptide-like and has a lower molecular weight than the initial MLL1 peptide. Therefore, compound 34 serves as a promising lead structure for the design of potent and cell-permeable inhibitors of the menin-MLL1 interaction.

PubMed: 23244744
DOI: 10.1021/jm3015298

実験手法

X-RAY DIFFRACTION (3.1 Å)