8DSF

Structure of cIAP1 with BCCov

8DSF の概要

• エントリーDOI: 10.2210/pdb8dsf/pdb
• 分子名称: Baculoviral IAP repeat-containing protein 2, ZINC ION, (4S)-4-[2-(2-{4-[(2E)-4-{(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}-4-oxobut-2-en-1-yl]piperazin-1-yl}ethoxy)acetamido]-1-{(2S)-2-cyclohexyl-2-[(N-methyl-L-alanyl)amino]acetyl}-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-L-prolinamide unbound form, ... (4 entities in total)
• 機能のキーワード: degrader, inhibitor of apoptosis, e3 ligase, apoptosis
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 49962.01

構造登録者

Schiemer, J.S.,Calabrese, M.F. (登録日: 2022-07-22, 公開日: 2023-03-08, 最終更新日: 2024-05-01)

主引用文献

Schiemer, J.,Maxwell, A.,Horst, R.,Liu, S.,Uccello, D.P.,Borzilleri, K.,Rajamohan, N.,Brown, M.F.,Calabrese, M.F.
A covalent BTK ternary complex compatible with targeted protein degradation.
Nat Commun, 14:1189-1189, 2023

PubMed Abstract: Targeted protein degradation using heterobifunctional chimeras holds the potential to expand target space and grow the druggable proteome. Most acutely, this provides an opportunity to target proteins that lack enzymatic activity or have otherwise proven intractable to small molecule inhibition. Limiting this potential, however, is the remaining need to develop a ligand for the target of interest. While a number of challenging proteins have been successfully targeted by covalent ligands, unless this modification affects form or function, it may lack the ability to drive a biological response. Bridging covalent ligand discovery with chimeric degrader design has emerged as a potential mechanism to advance both fields. In this work, we employ a set of biochemical and cellular tools to deconvolute the role of covalent modification in targeted protein degradation using Bruton's tyrosine kinase. Our results reveal that covalent target modification is fundamentally compatible with the protein degrader mechanism of action.

PubMed: 36864023
DOI: 10.1038/s41467-023-36738-z

実験手法

X-RAY DIFFRACTION (1.5 Å)