3QBR

BakBH3 in complex with sjA

3QBR の概要

• エントリーDOI: 10.2210/pdb3qbr/pdb
• 分子名称: SJCHGC06286 protein, Bcl-2 homologous antagonist/killer, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: helical bundle, bcl-2-like fold, apoptosis
• 由来する生物種: Schistosoma japonicum (Blood fluke); 詳細
• 細胞内の位置: Mitochondrion membrane ; Single-pass membrane protein : Q16611
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 48840.07

構造登録者

Lee, E.F.,Clarke, O.B.,Fairlie, W.D.,Colman, P.M.,Evangelista, M.,Feng, Z.,Speed, T.P.,Tchoubrieva, E.,Strasser, A.,Kalinna, B. (登録日: 2011-01-13, 公開日: 2011-04-13, 最終更新日: 2024-11-20)

主引用文献

Lee, E.F.,Clarke, O.B.,Evangelista, M.,Feng, Z.,Speed, T.P.,Tchoubrieva, E.B.,Strasser, A.,Kalinna, B.H.,Colman, P.M.,Fairlie, W.D.
Discovery and molecular characterization of a Bcl-2-regulated cell death pathway in schistosomes.
Proc.Natl.Acad.Sci.USA, 108:6999-7003, 2011

PubMed Abstract: Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2-regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2-like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with "BH3 mimetic" drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.

PubMed: 21444803
DOI: 10.1073/pnas.1100652108

実験手法

X-RAY DIFFRACTION (2.601 Å)