8B5C

Human BRD4 bromdomain 1 in complex with a H4 peptide containing ApmTri (H4K5/8ApmTri)

8B5C の概要

• エントリーDOI: 10.2210/pdb8b5c/pdb
• 分子名称: Bromodomain-containing protein 4, H4K5/8ApmTri (3 entities in total)
• 機能のキーワード: apmtri, acetyl-lysine mimic, bet-bromodomain, histone-peptide, peptide binding protein
• 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: 16556.02

構造登録者

Braun, M.B.,Bartlick, N.,Stehle, T. (登録日: 2022-09-22, 公開日: 2023-01-11, 最終更新日: 2024-11-20)

主引用文献

Kirchgassner, S.,Braun, M.B.,Bartlick, N.,Koc, C.,Reinkemeier, C.D.,Lemke, E.A.,Stehle, T.,Schwarzer, D.
Synthesis, Biochemical Characterization, and Genetic Encoding of a 1,2,4-Triazole Amino Acid as an Acetyllysine Mimic for Bromodomains of the BET Family.
Angew.Chem.Int.Ed.Engl., 62:e202215460-e202215460, 2023

PubMed Abstract: Lysine acetylation is a charge-neutralizing post-translational modification of proteins bound by bromodomains (Brds). A 1,2,4-triazole amino acid (ApmTri) was established as acetyllysine (Kac) mimic recruiting Brds of the BET family in contrast to glutamine commonly used for simulating this modification. Optimization of triazole substituents and side chain spacing allowed BET Brd recruitment to ApmTri-containing peptides with affinities similar to native substrates. Crystal structures of ApmTri-containing peptides in complex with two BET Brds revealed the binding mode which mirrored that of Kac ligands. ApmTri was genetically encoded and recombinant ApmTri-containing proteins co-enriched BRD3(2) from cellular lysates. This interaction was blocked by BET inhibitor JQ1. With genetically encoded ApmTri, biochemistry is now provided with a stable Kac mimic reflecting charge neutralization and Brd recruitment, allowing new investigations into BET proteins in vitro and in vivo.

PubMed: 36585954
DOI: 10.1002/anie.202215460

実験手法

X-RAY DIFFRACTION (1.58 Å)