3MUP

cIAP1-BIR3 domain in complex with the Smac-mimetic compound Smac037

3MUP の概要

• エントリーDOI: 10.2210/pdb3mup/pdb
• 関連するPDBエントリー: 3EYL 3OZ1
• 分子名称: Baculoviral IAP repeat-containing protein 2, (3S,6S,7R,9aS)-6-{[(2S)-2-aminobutanoyl]amino}-7-(2-aminoethyl)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: zinc-finger motif, apoptosis inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q13490
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 59845.21

構造登録者

Cossu, F.,Malvezzi, F.,Canevari, G.,Milani, M. (登録日: 2010-05-03, 公開日: 2010-11-24, 最終更新日: 2023-11-01)

主引用文献

Cossu, F.,Malvezzi, F.,Canevari, G.,Mastrangelo, E.,Lecis, D.,Delia, D.,Seneci, P.,Scolastico, C.,Bolognesi, M.,Milani, M.
Recognition of Smac-mimetic compounds by the BIR domain of cIAP1
Protein Sci., 19:2418-2429, 2010

PubMed Abstract: Inhibitor of apoptosis proteins (IAPs) are negative regulators of apoptosis. As IAPs are overexpressed in many tumors, where they confer chemoresistance, small molecules inactivating IAPs have been proposed as anticancer agents. Accordingly, a number of IAP-binding pro-apoptotic compounds that mimic the sequence corresponding to the N-terminal tetrapeptide of Smac/DIABLO, the natural endogenous IAPs inhibitor, have been developed. Here, we report the crystal structures of the BIR3 domain of cIAP1 in complex with Smac037, a Smac-mimetic known to bind potently to the XIAP-BIR3 domain and to induce degradation of cIAP1, and in complex with the novel Smac-mimetic compound Smac066. Thermal stability and fluorescence polarization assays show the stabilizing effect and the high affinity of both Smac037 and Smac066 for cIAP1- and cIAP2-BIR3 domains.

PubMed: 20954235
DOI: 10.1002/pro.523

実験手法

X-RAY DIFFRACTION (2.6 Å)