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| | ==Crystal structure of SAUGI/HSV UDG complex== | | ==Crystal structure of SAUGI/HSV UDG complex== |
| - | <StructureSection load='5ays' size='340' side='right' caption='[[5ays]], [[Resolution|resolution]] 2.09Å' scene=''> | + | <StructureSection load='5ays' size='340' side='right'caption='[[5ays]], [[Resolution|resolution]] 2.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ays]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AYS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ays]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1_strain_17 Human alphaherpesvirus 1 strain 17] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AYS FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ayr|5ayr]]</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]] 2.09Å</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=5ays FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ays OCA], [https://pdbe.org/5ays PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ays RCSB], [https://www.ebi.ac.uk/pdbsum/5ays PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ays 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=5ays FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ays OCA], [http://pdbe.org/5ays PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ays RCSB], [http://www.ebi.ac.uk/pdbsum/5ays 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5ays" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5ays" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Uracil-DNA glycosylase]] | + | [[Category: Human alphaherpesvirus 1 strain 17]] |
| - | [[Category: Huang, M F]] | + | [[Category: Large Structures]] |
| - | [[Category: Ko, T P]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Huang MF]] |
| - | [[Category: Wang, H C]] | + | [[Category: Ko TP]] |
| - | [[Category: Dna mimic protein]] | + | [[Category: Wang AHJ]] |
| - | [[Category: Dna mimicking]] | + | [[Category: Wang HC]] |
| - | [[Category: Herpes simplex virus]]
| + | |
| - | [[Category: Hydrolase inhibitor]]
| + | |
| - | [[Category: Uracil-dna glycosylase]]
| + | |
| - | [[Category: Uracil-dna glycosylase inhibitor]]
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| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
Uracil-DNA glycosylases (UDGs) are highly conserved proteins that can be found in a wide range of organisms, and are involved in the DNA repair and host defense systems. UDG activity is controlled by various cellular factors, including the uracil-DNA glycosylase inhibitors, which are DNA mimic proteins that prevent the DNA binding sites of UDGs from interacting with their DNA substrate. To date, only three uracil-DNA glycosylase inhibitors, phage UGI, p56, and Staphylococcus aureus SAUGI, have been determined. We show here that SAUGI has differential inhibitory effects on UDGs from human, bacteria, Herpes simplex virus (HSV; human herpesvirus 1) and Epstein-Barr virus (EBV; human herpesvirus 4). Newly determined crystal structures of SAUGI/human UDG and a SAUGI/HSVUDG complex were used to explain the differential binding activities of SAUGI on these two UDGs. Structural-based protein engineering was further used to modulate the inhibitory ability of SAUGI on human UDG and HSVUDG. The results of this work extend our understanding of DNA mimics as well as potentially opening the way for novel therapeutic applications for this kind of protein.
Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase.,Wang HC, Ho CH, Chou CC, Ko TP, Huang MF, Hsu KC, Wang AH Nucleic Acids Res. 2016 May 19;44(9):4440-9. doi: 10.1093/nar/gkw185. Epub 2016, Mar 14. PMID:26980279[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Savva R, Pearl LH. Nucleotide mimicry in the crystal structure of the uracil-DNA glycosylase-uracil glycosylase inhibitor protein complex. Nat Struct Biol. 1995 Sep;2(9):752-7. PMID:7552746
- ↑ Krusong K, Carpenter EP, Bellamy SR, Savva R, Baldwin GS. A comparative study of uracil-DNA glycosylases from human and herpes simplex virus type 1. J Biol Chem. 2006 Feb 24;281(8):4983-92. Epub 2005 Nov 22. PMID:16306042 doi:http://dx.doi.org/10.1074/jbc.M509137200
- ↑ Wang HC, Ho CH, Chou CC, Ko TP, Huang MF, Hsu KC, Wang AH. Using structural-based protein engineering to modulate the differential inhibition effects of SAUGI on human and HSV uracil DNA glycosylase. Nucleic Acids Res. 2016 May 19;44(9):4440-9. doi: 10.1093/nar/gkw185. Epub 2016, Mar 14. PMID:26980279 doi:http://dx.doi.org/10.1093/nar/gkw185
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