8BR9

Stapled peptide SP24 in complex with humanised RadA mutant HumRadA22

8BR9 の概要

• エントリーDOI: 10.2210/pdb8br9/pdb
• 分子名称: DNA repair and recombination protein RadA, Breast cancer type 2 susceptibility protein, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: stapled peptide, rad51, brca2, brc repeat, recombination
• 由来する生物種: Pyrococcus furiosus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30105.97

構造登録者

Pantelejevs, T.,Hyvonen, M. (登録日: 2022-11-22, 公開日: 2023-03-08, 最終更新日: 2024-11-13)

主引用文献

Pantelejevs, T.,Zuazua-Villar, P.,Koczy, O.,Counsell, A.J.,Walsh, S.J.,Robertson, N.S.,Spring, D.R.,Downs, J.A.,Hyvonen, M.
A recombinant approach for stapled peptide discovery yields inhibitors of the RAD51 recombinase.
Chem Sci, 14:13915-13923, 2023

PubMed Abstract: Stapling is a macrocyclisation method that connects amino acid side chains of a peptide to improve its pharmacological properties. We describe an approach for stapled peptide preparation and biochemical evaluation that combines recombinant expression of fusion constructs of target peptides and cysteine-reactive divinyl-heteroaryl chemistry as an alternative to solid-phase synthesis. We then employ this workflow to prepare and evaluate BRC-repeat-derived inhibitors of the RAD51 recombinase, showing that a diverse range of secondary structure elements in the BRC repeat can be stapled without compromising binding and function. Using X-ray crystallography, we elucidate the atomic-level features of the staple moieties. We then demonstrate that BRC-repeat-derived stapled peptides can disrupt RAD51 function in cells following ionising radiation treatment.

PubMed: 38075664
DOI: 10.1039/d3sc03331g

実験手法

X-RAY DIFFRACTION (1.63 Å)