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| | ==Crystal structure of the vaccinia virus DNA polymerase holoenzyme subunit D4 in complex with the A20 N-terminus== | | ==Crystal structure of the vaccinia virus DNA polymerase holoenzyme subunit D4 in complex with the A20 N-terminus== |
| - | <StructureSection load='4od8' size='340' side='right' caption='[[4od8]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='4od8' size='340' side='right'caption='[[4od8]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4od8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Vaccc Vaccc]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OD8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OD8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4od8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus_Copenhagen Vaccinia virus Copenhagen]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OD8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oda|4oda]]</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=4od8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4od8 OCA], [https://pdbe.org/4od8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4od8 RCSB], [https://www.ebi.ac.uk/pdbsum/4od8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4od8 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">D4R, UNG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10249 VACCC]), A20R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10249 VACCC])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Uracil-DNA_glycosylase Uracil-DNA glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.27 3.2.2.27] </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=4od8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4od8 OCA], [http://pdbe.org/4od8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4od8 RCSB], [http://www.ebi.ac.uk/pdbsum/4od8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4od8 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UNG_VACCC UNG_VACCC]] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. Also part of a heterodimeric processivity factor which potentiates the DNA polymerase activity. Binds to DNA (By similarity). [[http://www.uniprot.org/uniprot/A20_VACCC A20_VACCC]] Plays an essential role in viral DNA replication by acting as the polymerase processivity factor together with protein D4. May serve as a bridge which links the DNA polymerase E9 and the uracil DNA glycosylase (By similarity). | + | [https://www.uniprot.org/uniprot/UNG_VACCC UNG_VACCC] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. Also part of a heterodimeric processivity factor which potentiates the DNA polymerase activity. Binds to DNA (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[DNA glycosylase|DNA glycosylase]] | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| - | *[[Uracil-DNA glycosylase|Uracil-DNA glycosylase]]
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Uracil-DNA glycosylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Vaccc]] | + | [[Category: Vaccinia virus Copenhagen]] |
| - | [[Category: Brazzolotto, X]] | + | [[Category: Brazzolotto X]] |
| - | [[Category: Burmeister, W P]] | + | [[Category: Burmeister WP]] |
| - | [[Category: Contesto-Richefeu, C]] | + | [[Category: Contesto-Richefeu C]] |
| - | [[Category: Iseni, F]] | + | [[Category: Iseni F]] |
| - | [[Category: Tarbouriech, N]] | + | [[Category: Tarbouriech N]] |
| - | [[Category: Dna binding]]
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| - | [[Category: Dna polymerase binding]]
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| - | [[Category: Dna polymerase processivity factor]]
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| - | [[Category: Hydrolase-replication complex]]
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| Structural highlights
Function
UNG_VACCC Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine. Also part of a heterodimeric processivity factor which potentiates the DNA polymerase activity. Binds to DNA (By similarity).
Publication Abstract from PubMed
Vaccinia virus polymerase holoenzyme is composed of the DNA polymerase E9, the uracil-DNA glycosylase D4 and A20, a protein with no known enzymatic activity. The D4/A20 heterodimer is the DNA polymerase co-factor whose function is essential for processive DNA synthesis. Genetic and biochemical data have established that residues located in the N-terminus of A20 are critical for binding to D4. However, no information regarding the residues of D4 involved in A20 binding is yet available. We expressed and purified the complex formed by D4 and the first 50 amino acids of A20 (D4/A201-50). We showed that whereas D4 forms homodimers in solution when expressed alone, D4/A201-50 clearly behaves as a heterodimer. The crystal structure of D4/A201-50 solved at 1.85 A resolution reveals that the D4/A20 interface (including residues 167 to 180 and 191 to 206 of D4) partially overlaps the previously described D4/D4 dimer interface. A201-50 binding to D4 is mediated by an alpha-helical domain with important leucine residues located at the very N-terminal end of A20 and a second stretch of residues containing Trp43 involved in stacking interactions with Arg167 and Pro173 of D4. Point mutations of the latter residues disturb D4/A201-50 formation and reduce significantly thermal stability of the complex. Interestingly, small molecule docking with anti-poxvirus inhibitors selected to interfere with D4/A20 binding could reproduce several key features of the D4/A201-50 interaction. Finally, we propose a model of D4/A201-50 in complex with DNA and discuss a number of mutants described in the literature, which affect DNA synthesis. Overall, our data give new insights into the assembly of the poxvirus DNA polymerase cofactor and may be useful for the design and rational improvement of antivirals targeting the D4/A20 interface.
Crystal structure of the vaccinia virus DNA polymerase holoenzyme subunit d4 in complex with the a20 N-terminal domain.,Contesto-Richefeu C, Tarbouriech N, Brazzolotto X, Betzi S, Morelli X, Burmeister WP, Iseni F PLoS Pathog. 2014 Mar 6;10(3):e1003978. doi: 10.1371/journal.ppat.1003978., eCollection 2014 Mar. PMID:24603707[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Contesto-Richefeu C, Tarbouriech N, Brazzolotto X, Betzi S, Morelli X, Burmeister WP, Iseni F. Crystal structure of the vaccinia virus DNA polymerase holoenzyme subunit d4 in complex with the a20 N-terminal domain. PLoS Pathog. 2014 Mar 6;10(3):e1003978. doi: 10.1371/journal.ppat.1003978., eCollection 2014 Mar. PMID:24603707 doi:http://dx.doi.org/10.1371/journal.ppat.1003978
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