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2xpx

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Revision as of 12:16, 22 July 2020

Crystal structure of BHRF1:Bak BH3 complex

Structural highlights

2xpx is a 2 chain structure with sequence from Ebvg and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1bxl, 2jcn, 2jby, 1q59
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[EAR_EBVB9] 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. [BAK_HUMAN] In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.^[1] ^[2]

Publication Abstract from PubMed

Epstein-Barr virus (EBV) is associated with human malignancies, especially those affecting the B cell compartment such as Burkitt lymphoma. The virally encoded homolog of the mammalian pro-survival protein Bcl-2, BHRF1 contributes to viral infectivity and lymphomagenesis. In addition to the pro-apoptotic BH3-only protein Bim, its key target in lymphoid cells, BHRF1 also binds a selective sub-set of pro-apoptotic proteins (Bid, Puma, Bak) expressed by host cells. A consequence of BHRF1 expression is marked resistance to a range of cytotoxic agents and in particular, we show that its expression renders a mouse model of Burkitt lymphoma untreatable. As current small organic antagonists of Bcl-2 do not target BHRF1, the structures of it in complex with Bim or Bak shown here will be useful to guide efforts to target BHRF1 in EBV-associated malignancies, which are usually associated with poor clinical outcomes.

Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1.,Kvansakul M, Wei AH, Fletcher JI, Willis SN, Chen L, Roberts AW, Huang DC, Colman PM PLoS Pathog. 2010 Dec 23;6(12):e1001236. PMID:21203485^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995 Nov 15;14(22):5589-96. PMID:8521816
↑ Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014
↑ Kvansakul M, Wei AH, Fletcher JI, Willis SN, Chen L, Roberts AW, Huang DC, Colman PM. Structural Basis for Apoptosis Inhibition by Epstein-Barr Virus BHRF1. PLoS Pathog. 2010 Dec 23;6(12):e1001236. PMID:21203485 doi:10.1371/journal.ppat.1001236

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xpx"

@@ Line 1: / Line 1: @@
 ==Crystal structure of BHRF1:Bak BH3 complex==
-<StructureSection load='2xpx' size='340' side='right' caption='[[2xpx]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
+<StructureSection load='2xpx' size='340' side='right'caption='[[2xpx]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xpx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebvg Ebvg] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XPX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xpx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebvg Ebvg] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XPX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XPX 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>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bxl|1bxl]], [[2jcn|2jcn]], [[2jby|2jby]], [[1q59|1q59]]</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=2xpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xpx OCA], [http://pdbe.org/2xpx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xpx RCSB], [http://www.ebi.ac.uk/pdbsum/2xpx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xpx ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2xpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xpx OCA], [http://pdbe.org/2xpx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xpx RCSB], [http://www.ebi.ac.uk/pdbsum/2xpx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xpx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[B-cell lymphoma protein|B-cell lymphoma protein]]
+*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
 == References ==
 <references/>
@@ Line 28: / Line 28: @@
 [[Category: Ebvg]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Colman, P M]]
 [[Category: Huang, D C.S]]

2xpx

From Proteopedia

Revision as of 12:16, 22 July 2020

Crystal structure of BHRF1:Bak BH3 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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