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| | <StructureSection load='1r6n' size='340' side='right'caption='[[1r6n]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1r6n' size='340' side='right'caption='[[1r6n]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1r6n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hpv_11 Hpv 11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1R6N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1r6n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_11 Human papillomavirus 11]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R6N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R6N FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=434:SPIRO[3-CARBOXY-4-{(4-[1,2,3]THIADIAZOL-4-YL-PHENYL)-AMINO-CARBONYL}+-5-[3,4-DICHLORO-PHENYL]-TETRAHYDROFURAN-2,2-5-METHYL-INDAN-1,3-DIONE]'>434</scene>, <scene name='pdbligand=ALQ:2-METHYL-PROPIONIC+ACID'>ALQ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=434:SPIRO[3-CARBOXY-4-{(4-[1,2,3]THIADIAZOL-4-YL-PHENYL)-AMINO-CARBONYL}+-5-[3,4-DICHLORO-PHENYL]-TETRAHYDROFURAN-2,2-5-METHYL-INDAN-1,3-DIONE]'>434</scene>, <scene name='pdbligand=ALQ:2-METHYL-PROPIONIC+ACID'>ALQ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1r6k|1r6k]]</div></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=1r6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6n OCA], [https://pdbe.org/1r6n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r6n RCSB], [https://www.ebi.ac.uk/pdbsum/1r6n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6n ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10580 HPV 11])</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=1r6n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r6n OCA], [http://pdbe.org/1r6n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1r6n RCSB], [http://www.ebi.ac.uk/pdbsum/1r6n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1r6n ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VE2_HPV11 VE2_HPV11]] E2 regulates viral transcription and DNA replication. It binds to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory region. It can either activate or repress transcription depending on E2RE's position with regards to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E1-E2 complex binds to the origin of DNA replication. | + | [https://www.uniprot.org/uniprot/VE2_HPV11 VE2_HPV11] E2 regulates viral transcription and DNA replication. It binds to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory region. It can either activate or repress transcription depending on E2RE's position with regards to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E1-E2 complex binds to the origin of DNA replication. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1r6n" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1r6n" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Regulatory protein E2|Regulatory protein E2]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hpv 11]] | + | [[Category: Human papillomavirus 11]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Coulombe, R]] | + | [[Category: Coulombe R]] |
| - | [[Category: Wang, Y]] | + | [[Category: Wang Y]] |
| - | [[Category: E2 tad]]
| + | |
| - | [[Category: Papillomavirus]]
| + | |
| - | [[Category: Replication]]
| + | |
| - | [[Category: Tad]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: X-ray structure]]
| + | |
| Structural highlights
Function
VE2_HPV11 E2 regulates viral transcription and DNA replication. It binds to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory region. It can either activate or repress transcription depending on E2RE's position with regards to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E1-E2 complex binds to the origin of DNA replication.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Interaction between the E2 protein and E1 helicase of human papillomaviruses (HPVs) is essential for the initiation of viral DNA replication. We recently described a series of small molecules that bind to the N-terminal transactivation domain (TAD) of HPV type 11 E2 and inhibits its interaction with E1 in vitro and in cellular assays. Here we report the crystal structures of both the HPV11 TAD and of a complex between this domain and an inhibitor, at 2.5- and 2.4-A resolution, respectively. The HPV11 TAD structure is very similar to that of the analogous domain of HPV16. Inhibitor binding caused no significant alteration of the protein backbone, but movements of several amino acid side chains at the binding site, in particular those of Tyr-19, His-32, Leu-94, and Glu-100, resulted in the formation of a deep hydrophobic pocket that accommodates the indandione moiety of the inhibitor. Mutational analysis provides functional evidence for specific interactions between Tyr-19 and E1 and between His-32 and the inhibitor. A second inhibitor molecule is also present at the binding pocket. Although evidence is presented that this second molecule makes only weak interactions with the protein and is likely an artifact of crystallization, its presence defines additional regions of the binding pocket that could be exploited to design more potent inhibitors.
Crystal structure of the E2 transactivation domain of human papillomavirus type 11 bound to a protein interaction inhibitor.,Wang Y, Coulombe R, Cameron DR, Thauvette L, Massariol MJ, Amon LM, Fink D, Titolo S, Welchner E, Yoakim C, Archambault J, White PW J Biol Chem. 2004 Feb 20;279(8):6976-85. Epub 2003 Nov 22. PMID:14634007[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang Y, Coulombe R, Cameron DR, Thauvette L, Massariol MJ, Amon LM, Fink D, Titolo S, Welchner E, Yoakim C, Archambault J, White PW. Crystal structure of the E2 transactivation domain of human papillomavirus type 11 bound to a protein interaction inhibitor. J Biol Chem. 2004 Feb 20;279(8):6976-85. Epub 2003 Nov 22. PMID:14634007 doi:10.1074/jbc.M311376200
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