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| | ==Crystal structure of a computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein== | | ==Crystal structure of a computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein== |
| - | <StructureSection load='4oyd' size='340' side='right' caption='[[4oyd]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='4oyd' size='340' side='right'caption='[[4oyd]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4oyd]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebva8 Ebva8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OYD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OYD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4oyd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Epstein-barr_virus_strain_ag876 Epstein-barr virus strain ag876] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OYD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OYD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BHRF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=82830 EBVA8])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4oyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oyd OCA], [https://pdbe.org/4oyd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oyd RCSB], [https://www.ebi.ac.uk/pdbsum/4oyd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oyd ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4oyd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oyd OCA], [http://pdbe.org/4oyd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oyd RCSB], [http://www.ebi.ac.uk/pdbsum/4oyd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oyd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EAR_EBVA8 EAR_EBVA8]] Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell (By similarity). | + | [https://www.uniprot.org/uniprot/EAR_EBVA8 EAR_EBVA8] Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ebva8]] | + | [[Category: Epstein-barr virus strain ag876]] |
| - | [[Category: Baker, D]] | + | [[Category: Large Structures]] |
| - | [[Category: Procko, E]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Shen, B]] | + | [[Category: Baker D]] |
| - | [[Category: Stoddard, B]] | + | [[Category: Procko E]] |
| - | [[Category: Apoptosis]] | + | [[Category: Shen B]] |
| - | [[Category: Complex]] | + | [[Category: Stoddard B]] |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Viral protein-inhibitor complex]]
| + | |
| Structural highlights
Function
EAR_EBVA8 Prevents premature death of the host cell during virus production, which would otherwise reduce the amount of progeny virus. Acts as a host B-cell leukemia/lymphoma 2 (Bcl-2) homolog, and interacts with pro-apoptotic proteins to prevent mitochondria permeabilization, release of cytochrome c and subsequent apoptosis of the host cell (By similarity).
Publication Abstract from PubMed
Because apoptosis of infected cells can limit virus production and spread, some viruses have co-opted prosurvival genes from the host. This includes the Epstein-Barr virus (EBV) gene BHRF1, a homolog of human Bcl-2 proteins that block apoptosis and are associated with cancer. Computational design and experimental optimization were used to generate a novel protein called BINDI that binds BHRF1 with picomolar affinity. BINDI recognizes the hydrophobic cleft of BHRF1 in a manner similar to other Bcl-2 protein interactions but makes many additional contacts to achieve exceptional affinity and specificity. BINDI induces apoptosis in EBV-infected cancer lines, and when delivered with an antibody-targeted intracellular delivery carrier, BINDI suppressed tumor growth and extended survival in a xenograft disease model of EBV-positive human lymphoma. High-specificity-designed proteins that selectively kill target cells may provide an advantage over the toxic compounds used in current generation antibody-drug conjugates.
A computationally designed inhibitor of an epstein-barr viral bcl-2 protein induces apoptosis in infected cells.,Procko E, Berguig GY, Shen BW, Song Y, Frayo S, Convertine AJ, Margineantu D, Booth G, Correia BE, Cheng Y, Schief WR, Hockenbery DM, Press OW, Stoddard BL, Stayton PS, Baker D Cell. 2014 Jun 19;157(7):1644-56. doi: 10.1016/j.cell.2014.04.034. PMID:24949974[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Procko E, Berguig GY, Shen BW, Song Y, Frayo S, Convertine AJ, Margineantu D, Booth G, Correia BE, Cheng Y, Schief WR, Hockenbery DM, Press OW, Stoddard BL, Stayton PS, Baker D. A computationally designed inhibitor of an epstein-barr viral bcl-2 protein induces apoptosis in infected cells. Cell. 2014 Jun 19;157(7):1644-56. doi: 10.1016/j.cell.2014.04.034. PMID:24949974 doi:http://dx.doi.org/10.1016/j.cell.2014.04.034
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