8CV6

Peptide 4.2B in complex with BRD4.2

8CV6 の概要

• エントリーDOI: 10.2210/pdb8cv6/pdb
• 分子名称: BRD4 protein, Peptide 4.2E, ACETYL GROUP, ... (5 entities in total)
• 機能のキーワード: cyclic peptide inhibitor bromodomain, transcription
• 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: 16351.91

構造登録者

Franck, C.,Mackay, J.P. (登録日: 2022-05-18, 公開日: 2023-05-24, 最終更新日: 2023-12-06)

主引用文献

Franck, C.,Patel, K.,Walport, L.J.,Christie, M.,Norman, A.,Passioura, T.,Suga, H.,Payne, R.J.,Mackay, J.P.
Discovery and characterization of cyclic peptides selective for the C-terminal bromodomains of BET family proteins.
Structure, 31:912-923.e4, 2023

PubMed Abstract: DNA-encoded cyclic peptide libraries can yield high-potency, high-specificity ligands against target proteins. We used such a library to seek ligands that could distinguish between paralogous bromodomains from the closely related bromodomain and extra-terminal domain family of epigenetic regulators. Several peptides isolated from a screen against the C-terminal bromodomain of BRD2, together with new peptides discovered in previous screens against the corresponding domain from BRD3 and BRD4, bound their targets with nanomolar and sub-nanomolar affinities. X-ray crystal structures of several of these bromodomain-peptide complexes reveal diverse structures and binding modes, which nevertheless display several conserved features. Some peptides demonstrate significant paralog-level specificity, although the physicochemical explanations for this specificity are often not clear. Our data demonstrate the power of cyclic peptides to discriminate between very similar proteins with high potency and hint that differences in conformational dynamics might modulate the affinity of these domains for particular ligands.

PubMed: 37269828
DOI: 10.1016/j.str.2023.05.009

実験手法

X-RAY DIFFRACTION (1.7 Å)