3QBR
BakBH3 in complex with sjA
Summary for 3QBR
| Entry DOI | 10.2210/pdb3qbr/pdb |
| Descriptor | SJCHGC06286 protein, Bcl-2 homologous antagonist/killer, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (4 entities in total) |
| Functional Keywords | helical bundle, bcl-2-like fold, apoptosis |
| Biological source | Schistosoma japonicum (Blood fluke) More |
| Cellular location | Mitochondrion membrane ; Single-pass membrane protein : Q16611 |
| Total number of polymer chains | 4 |
| Total formula weight | 48840.07 |
| Authors | 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. (deposition date: 2011-01-13, release date: 2011-04-13, Last modification date: 2024-11-20) |
| Primary citation | 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 Cited by 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: 21444803DOI: 10.1073/pnas.1100652108 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.601 Å) |
Structure validation
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