4BEA

Crystal Structure of eIF4E in Complex with a Stapled Peptide Derivative

4BEA の概要

• エントリーDOI: 10.2210/pdb4bea/pdb
• 分子名称: Eukaryotic translation initiation factor 4E, STAPLED EIF4E INTERACTING PEPTIDE (3 entities in total)
• 機能のキーワード: translation
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, P-body : P06730
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26691.23

構造登録者

Quah, S.T.,Lama, D.,Verma, C.S.,Lane, D.P.,Brown, C.J. (登録日: 2013-03-07, 公開日: 2013-12-11, 最終更新日: 2024-10-16)

主引用文献

Lama, D.,Quah, S.T.,Verma, C.S.,Lakshminarayanan, R.,Beuerman, R.W.,Lane, D.P.,Brown, C.J.
Rational Optimization of Conformational Effects Induced by Hydrocarbon Staples in Peptides and Their Binding Interfaces.
Sci.Rep., 3:3451-, 2013

PubMed Abstract: eIF4E is frequently over-expressed in different cancers and causes increased translation of oncogenic proteins via deregulated cap-dependent translation. Inhibitors of the eIF4E:eIF4G interactions represent an approach that would normalize cap-dependent translation. Stapled peptides represent an emerging class of therapeutics that can target protein: protein interactions. We present here molecular dynamics simulations for a set of rationally designed stapled peptides in solution and in complex with eIF4E, supported with biophysical and crystallographic data. Clustering of the simulated structures revealed the favoured conformational states of the stapled peptides in their bound or free forms in solution. Identifying these populations has allowed us to design peptides with improved affinities by introducing mutations into the peptide sequence to alter their conformational distributions. These studies emphasise the effects that engineered mutations have on the conformations of free and bound peptides, and illustrate that both states must be considered in efforts to attain high affinity binding.

PubMed: 24336354
DOI: 10.1038/SREP03451

実験手法

X-RAY DIFFRACTION (2.57 Å)