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4oyd

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Revision as of 09:03, 1 November 2017

Crystal structure of a computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein

Structural highlights

4oyd is a 4 chain structure with sequence from Ebva8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	BHRF1 (EBVA8)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4oyd"

@@ Line 3: / Line 3: @@
 <StructureSection load='4oyd' size='340' side='right' caption='[[4oyd]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4oyd]] is a 4 chain structure. 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 [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>
 </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>
+<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'>[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>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Ebva8]]
 [[Category: Baker, D]]
 [[Category: Procko, E]]

4oyd

From Proteopedia

Revision as of 09:03, 1 November 2017

Crystal structure of a computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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