6OPJ

Menin in complex with peptide inhibitor 25

6OPJ の概要

• エントリーDOI: 10.2210/pdb6opj/pdb
• 分子名称: Menin, Peptide inhibitor 25, DIMETHYL SULFOXIDE, ... (6 entities in total)
• 機能のキーワード: protein-protein interaction inhibitor, protein binding-inhibitor complex, protein binding/inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 56878.96

構造登録者

Linhares, B.M.,Fortuna, P.,Cierpicki, T.,Grembecka, J.,Berlicki, L. (登録日: 2019-04-25, 公開日: 2020-09-02, 最終更新日: 2023-11-15)

主引用文献

Fortuna, P.,Linhares, B.M.,Purohit, T.,Pollock, J.,Cierpicki, T.,Grembecka, J.,Berlicki, L.
Covalent and noncovalent constraints yield a figure eight-like conformation of a peptide inhibiting the menin-MLL interaction.
Eur.J.Med.Chem., 207:112748-112748, 2020

PubMed Abstract: The interaction between menin and mixed lineage leukemia (MLL) was identified as an interesting target for treating some cancers including acute leukemia. On the basis of the known crystal structure of the MBM1-menin complex (MBM - menin binding motif), several cyclic peptides were designed. Elaboration of the effective cyclization strategy using a metathesis reaction allowed for a successfully large number of derivatives to be obtained. Subsequent optimization of the loop size, as well as N-terminal, central and C-terminal parts of the studied peptides resulted in structures exhibiting low nanomolar activities. A crystal structure of an inhibitor-menin complex revealed a compact conformation of the ligand molecule, which is stabilized not only by the introduction of a covalent linker but also three intramolecular hydrogen bonds. The inhibitor adopts a figure eight-like conformation, which perfectly fits the cleft of menin. We demonstrated that the development of compact, miniprotein-like structures is a highly effective approach for inhibition of protein-protein interactions.

PubMed: 32882610
DOI: 10.1016/j.ejmech.2020.112748

実験手法

X-RAY DIFFRACTION (1.50065718427 Å)