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| ==Crystallographic Structure of HHV-1 Uracil-DNA Glycosylase complexed with the Bacillus phage PZA inhibitor protein p56== | | ==Crystallographic Structure of HHV-1 Uracil-DNA Glycosylase complexed with the Bacillus phage PZA inhibitor protein p56== |
| <StructureSection load='4l5n' size='340' side='right' caption='[[4l5n]], [[Resolution|resolution]] 2.16Å' scene=''> | | <StructureSection load='4l5n' size='340' side='right'caption='[[4l5n]], [[Resolution|resolution]] 2.16Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4l5n]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_phage_pza Bacillus phage pza] and [http://en.wikipedia.org/wiki/Herpes_simplex_virus_(type_1_/_strain_17) Herpes simplex virus (type 1 / strain 17)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L5N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L5N FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4l5n]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_phage_PZA Bacillus phage PZA] and [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_17 Human alphaherpesvirus 1 strain 17]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L5N FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.16Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10299 Herpes simplex virus (type 1 / strain 17)]), 1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10757 Bacillus phage PZA])</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| <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'>[https://proteopedia.org/fgij/fg.htm?mol=4l5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l5n OCA], [https://pdbe.org/4l5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l5n RCSB], [https://www.ebi.ac.uk/pdbsum/4l5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l5n ProSAT]</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=4l5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l5n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l5n RCSB], [http://www.ebi.ac.uk/pdbsum/4l5n PDBsum]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/UNG_HHV11 UNG_HHV11]] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly, in terminally differentiated neurons which lack DNA repair enzymes.<ref>PMID:7552746</ref> <ref>PMID:16306042</ref> | | [https://www.uniprot.org/uniprot/UNG_HHV11 UNG_HHV11] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosine. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly, in terminally differentiated neurons which lack DNA repair enzymes.<ref>PMID:7552746</ref> <ref>PMID:16306042</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Uracil-DNA glycosylase (UDG) compromises the replication strategies of diverse viruses from unrelated lineages. Virally encoded proteins therefore exist to limit, inhibit or target UDG activity for proteolysis. Viral proteins targeting UDG, such as the bacteriophage proteins ugi, and p56, and the HIV-1 protein Vpr, share no sequence similarity, and are not structurally homologous. Such diversity has hindered identification of known or expected UDG-inhibitory activities in other genomes. The structural basis for UDG inhibition by ugi is well characterized; yet, paradoxically, the structure of the unbound p56 protein is enigmatically unrevealing of its mechanism. To resolve this conundrum, we determined the structure of a p56 dimer bound to UDG. A helix from one of the subunits of p56 occupies the UDG DNA-binding cleft, whereas the dimer interface forms a hydrophobic box to trap a mechanistically important UDG residue. Surprisingly, these p56 inhibitory elements are unexpectedly analogous to features used by ugi despite profound architectural disparity. Contacts from B-DNA to UDG are mimicked by residues of the p56 helix, echoing the role of ugi's inhibitory beta strand. Using mutagenesis, we propose that DNA mimicry by p56 is a targeting and specificity mechanism supporting tight inhibition via hydrophobic sequestration.
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| Architecturally diverse proteins converge on an analogous mechanism to inactivate Uracil-DNA glycosylase.,Cole AR, Ofer S, Ryzhenkova K, Baltulionis G, Hornyak P, Savva R Nucleic Acids Res. 2013 Jul 26. PMID:23892286<ref>PMID:23892286</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| ==See Also== | | ==See Also== |
| *[[Uracil-DNA glycosylase|Uracil-DNA glycosylase]] | | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bacillus phage pza]] | | [[Category: Bacillus phage PZA]] |
| [[Category: Uracil-DNA glycosylase]] | | [[Category: Human alphaherpesvirus 1 strain 17]] |
| [[Category: Baltulionis, G]] | | [[Category: Large Structures]] |
| [[Category: Cole, A R]] | | [[Category: Baltulionis G]] |
| [[Category: Hornyak, P]] | | [[Category: Cole AR]] |
| [[Category: Ryzhenkova, K]] | | [[Category: Hornyak P]] |
| [[Category: Sapir, O]] | | [[Category: Ryzhenkova K]] |
| [[Category: Savva, R]] | | [[Category: Sapir O]] |
| [[Category: Hydrolase-hydrolase inhibitor complex]]
| | [[Category: Savva R]] |
| [[Category: Udg inhibition]]
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