5DXE

Estrogen Receptor Alpha Ligand Binding Domain Y537S Mutant in Complex with Stapled Peptide SRC2-P4 and Estradiol

5DXE の概要

• エントリーDOI: 10.2210/pdb5dxe/pdb
• 分子名称: Estrogen receptor, Nuclear receptor coactivator 2, ESTRADIOL, ... (4 entities in total)
• 機能のキーワード: estrogen receptor alpha, stapled peptide, peptide mimetic, breast cancer, hormone, somatic mutation, hormone receptor-peptide complex, hormone receptor/peptide
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 63200.97

構造登録者

Fanning, S.W.,Speltz, T.E.,Mayne, C.G.,Tajkhorshid, E.,Greene, G.L.,Moore, T.W. (登録日: 2015-09-23, 公開日: 2016-08-03, 最終更新日: 2023-11-15)

主引用文献

Speltz, T.E.,Fanning, S.W.,Mayne, C.G.,Fowler, C.,Tajkhorshid, E.,Greene, G.L.,Moore, T.W.
Stapled Peptides with gamma-Methylated Hydrocarbon Chains for the Estrogen Receptor/Coactivator Interaction.
Angew.Chem.Int.Ed.Engl., 55:4252-4255, 2016

PubMed Abstract: "Stapled" peptides are typically designed to replace two non-interacting residues with a constraining, olefinic staple. To mimic interacting leucine and isoleucine residues, we have created new amino acids that incorporate a methyl group in the γ-position of the stapling amino acid S5. We have incorporated them into a sequence derived from steroid receptor coactivator 2, which interacts with estrogen receptor α. The best peptide (IC50 =89 nm) replaces isoleucine 689 with an S-γ-methyl stapled amino acid, and has significantly higher affinity than unsubstituted peptides (390 and 760 nm). Through X-ray crystallography and molecular dynamics studies, we show that the conformation taken up by the S-γ-methyl peptide minimizes the syn-pentane interactions between the α- and γ-methyl groups.

PubMed: 26928945
DOI: 10.1002/anie.201510557

実験手法

X-RAY DIFFRACTION (1.5 Å)