3EYL

Crystal structure of XIAP BIR3 domain in complex with a Smac-mimetic compound

3EYL の概要

• エントリーDOI: 10.2210/pdb3eyl/pdb
• 関連するPDBエントリー: 1g73 3clx 3cm2 3cm7
• 分子名称: Baculoviral IAP repeat-containing protein 4, ZINC ION, (3S,6S,7R,9aS)-6-{[(2S)-2-aminobutanoyl]amino}-7-(2-aminoethyl)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide, ... (4 entities in total)
• 機能のキーワード: apoptosis, smac-mimetics, zinc-finger, ligase, metal-binding, phosphoprotein, protease inhibitor, thiol protease inhibitor, ubl conjugation pathway
• 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: 2
• 化学式量合計: 29387.40

構造登録者

Cossu, F.,Milani, M.,Mastrangelo, E.,Bolognesi, M. (登録日: 2008-10-21, 公開日: 2008-11-25, 最終更新日: 2023-09-06)

主引用文献

Cossu, F.,Mastrangelo, E.,Milani, M.,Sorrentino, G.,Lecis, D.,Delia, D.,Manzoni, L.,Seneci, P.,Scolastico, C.,Bolognesi, M.
Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2.
Biochem.Biophys.Res.Commun., 378:162-167, 2009

PubMed Abstract: Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. Several compounds targeting IAPs and inducing cell death in cancer cells have been developed. Some of these are synthesized mimicking the N-terminal tetrapeptide sequence of Smac/DIABLO, the natural endogenous IAPs inhibitor. Starting from such conceptual design, we generated a library of 4-substituted azabicyclo[5.3.0]alkane Smac-mimetics. Here we report the crystal structure of the BIR3 domain from XIAP in complex with Smac037, a compound designed according to structural principles emerging from our previously analyzed XIAP BIR3/Smac-mimetic complexes. In parallel, we present an in silico docking analysis of three Smac-mimetics to the BIR3 domain of cIAP1, providing general considerations for the development of high affinity lead compounds targeting three members of the IAP family.

PubMed: 18992220
DOI: 10.1016/j.bbrc.2008.10.139

実験手法

X-RAY DIFFRACTION (3 Å)