4ibf: Difference between revisions

Latest revision as of 11:52, 1 March 2024

Ebola virus VP35 bound to small molecule

Structural highlights

4ibf is a 2 chain structure with sequence from Ebola virus - Mayinga, Zaire, 1976. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.291Å
Ligands:	1D5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VP35_EBOZM Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.^[1] ^[2] ^[3] ^[4] ^[5]

References

↑ Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol. 1999 Mar;73(3):2333-42. PMID:9971816
↑ Basler CF, Wang X, Muhlberger E, Volchkov V, Paragas J, Klenk HD, Garcia-Sastre A, Palese P. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12289-94. PMID:11027311 doi:10.1073/pnas.220398297
↑ Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol. 2003 Jul;77(14):7945-56. PMID:12829834
↑ Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Muhlberger E. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006 Mar;50(3):984-93. PMID:16495261 doi:10.1128/AAC.50.3.984-993.2006
↑ Feng Z, Cerveny M, Yan Z, He B. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol. 2007 Jan;81(1):182-92. Epub 2006 Oct 25. PMID:17065211 doi:JVI.01006-06

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol. 1999 Mar;73(3):2333-42. PMID:9971816

[2] Basler CF, Wang X, Muhlberger E, Volchkov V, Paragas J, Klenk HD, Garcia-Sastre A, Palese P. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12289-94. PMID:11027311 doi:10.1073/pnas.220398297

[3] Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol. 2003 Jul;77(14):7945-56. PMID:12829834

[4] Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Muhlberger E. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006 Mar;50(3):984-93. PMID:16495261 doi:10.1128/AAC.50.3.984-993.2006

[5] Feng Z, Cerveny M, Yan Z, He B. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol. 2007 Jan;81(1):182-92. Epub 2006 Oct 25. PMID:17065211 doi:JVI.01006-06

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[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4ibf|  PDB=4ibf  |  SCENE=  }}
-===Ebola virus VP35 bound to small molecule===
-{{ABSTRACT_PUBMED_24495995}}
-==Function==
+==Ebola virus VP35 bound to small molecule==
-[[http://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM]] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
+<StructureSection load='4ibf' size='340' side='right'caption='[[4ibf]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
+== Structural highlights ==
-==About this Structure==
+<table><tr><td colspan='2'>[[4ibf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IBF FirstGlance]. <br>
-[[4ibf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBF OCA].
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.291&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1D5:(4-{(2R)-2-(4-BROMOTHIOPHEN-2-YL)-3-[(5-CHLOROTHIOPHEN-2-YL)CARBONYL]-4-HYDROXY-5-OXO-2,5-DIHYDRO-1H-PYRROL-1-YL}PHENYL)ACETIC+ACID'>1D5</scene></td></tr>
-==Reference==
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ibf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibf OCA], [https://pdbe.org/4ibf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ibf RCSB], [https://www.ebi.ac.uk/pdbsum/4ibf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibf ProSAT]</span></td></tr>
-<ref group="xtra">PMID:024495995</ref><references group="xtra"/><references/>
+</table>
-[[Category: Amarasinghe, G K.]]
+== Function ==
-[[Category: Binning, J M.]]
+[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
-[[Category: Borek, D M.]]
+== References ==
-[[Category: Brown, C S.]]
+<references/>
-[[Category: CSGID, Center for Structural Genomics of Infectious Diseases.]]
+__TOC__
-[[Category: Leung, D W.]]
+</StructureSection>
-[[Category: Otwinowski, Z.]]
+[[Category: Ebola virus - Mayinga, Zaire, 1976]]
-[[Category: Peterson, D S.]]
+[[Category: Large Structures]]
-[[Category: Ramanan, P.]]
+[[Category: Amarasinghe GK]]
-[[Category: Stubbs, A J.]]
+[[Category: Binning JM]]
-[[Category: Xu, W.]]
+[[Category: Borek DM]]
-[[Category: Center for structural genomics of infectious disease]]
+[[Category: Brown CS]]
-[[Category: Csgid]]
+[[Category: Leung DW]]
-[[Category: Interferon inhibitor domain]]
+[[Category: Otwinowski Z]]
-[[Category: National institute of allergy and infectious disease]]
+[[Category: Peterson DS]]
-[[Category: Niaid]]
+[[Category: Ramanan P]]
-[[Category: Structural genomic]]
+[[Category: Stubbs AJ]]
-[[Category: Transcription-transcription inhibitor complex]]
+[[Category: Xu W]]

4ibf: Difference between revisions

Latest revision as of 11:52, 1 March 2024

Ebola virus VP35 bound to small molecule

Structural highlights

Function

References

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