4OXC

Crystal structure of XIAP BIR1 domain

4OXC の概要

• エントリーDOI: 10.2210/pdb4oxc/pdb
• 関連するPDBエントリー: 4MTZ
• 分子名称: E3 ubiquitin-protein ligase XIAP, ZINC ION (3 entities in total)
• 機能のキーワード: xiap, bir, zn finger, ligase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P98170
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 49692.58

構造登録者

Milani, M.,Cossu, F.,Mastrangelo, E. (登録日: 2014-02-05, 公開日: 2015-02-11, 最終更新日: 2023-12-27)

主引用文献

Cossu, F.,Milani, M.,Grassi, S.,Malvezzi, F.,Corti, A.,Bolognesi, M.,Mastrangelo, E.
NF023 binding to XIAP-BIR1: Searching drugs for regulation of the NF-kappa B pathway.
Proteins, 83:612-620, 2015

PubMed Abstract: Inhibitor of Apoptosis Proteins (IAPs) are the target of extensive research in the field of cancer therapy since they regulate apoptosis and cell survival. Smac-mimetics, the most promising IAP-targeting compounds specifically recognize the IAP-BIR3 domain and promote apoptosis, competing with caspases for IAP binding. Furthermore, Smac-mimetics interfere with the NF-κB survival pathway, inducing cIAP1 and cIAP2 degradation through an auto-ubiquitination process. It has been shown that the XIAP-BIR1 (X-BIR1) domain is involved in the interaction with TAB1, an upstream adaptor for TAK1 kinase activation, which in turn couples with the NF-κB survival pathway. Preventing X-BIR1 dimerization abolishes XIAP-mediated NF-κB activation, thus implicating a proximity-induced mechanism for TAK1 activation. In this context, in a systematic search for a molecule capable of impairing X-BIR1/TAB1 assembly, we identified the compound NF023. Here we report the crystal structure of the human X-BIR1 domain in the absence and in the presence of NF023, as a starting concept for the design of novel BIR1-specific compounds acting synergistically with existing pro-apoptotic drugs in cancer therapy.

PubMed: 25619915
DOI: 10.1002/prot.24766

実験手法

X-RAY DIFFRACTION (2.9 Å)