6lyv: Difference between revisions
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The | ==The crystal structure of SAUGI/KSHVUDG complex== | ||
<StructureSection load='6lyv' size='340' side='right'caption='[[6lyv]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6lyv]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8] 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=6LYV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LYV FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</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=6lyv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lyv OCA], [https://pdbe.org/6lyv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lyv RCSB], [https://www.ebi.ac.uk/pdbsum/6lyv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lyv ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/UNG_HHV8P UNG_HHV8P] Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosines. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly in terminally differentiated cells which lack DNA repair enzymes.[HAMAP-Rule:MF_04046] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Uracil-DNA glycosylases (UDGs) are conserved DNA-repair enzymes that can be found in many species, including herpesviruses. Since they play crucial roles for efficient viral DNA replication in herpesviruses, they have been considered as potential antiviral targets. In our previous work, Staphylococcus aureus SAUGI was identified as a DNA mimic protein that targets UDGs from S. aureus, human, Herpes simplex virus (HSV) and Epstein-Barr virus (EBV). Interestingly, SAUGI has the strongest inhibitory effects with EBVUDG. Here, we determined complex structures of SAUGI with EBVUDG and another gamma-herpesvirus UDG from Kaposi's sarcoma-associated herpesvirus (KSHVUDG), which SAUGI fails to effectively inhibit. Structural analysis of the SAUGI/EBVUDG complex suggests that the additional interaction between SAUGI and the leucine loop may explain why SAUGI shows the highest binding capacity with EBVUDG. In contrast, SAUGI appears to make only partial contacts with the key components responsible for the compression and stabilization of the DNA backbone in the leucine loop extension of KSHVUDG. The findings in this study provide a molecular explanation for the differential inhibitory effects and binding strengths that SAUGI has on these two UDGs, and the structural basis of the differences should be helpful in developing inhibitors that would interfere with viral DNA replication. | |||
Structural insight into the differential interactions between the DNA mimic protein SAUGI and two gamma herpesvirus uracil-DNA glycosylases.,Liao YT, Lin SJ, Ko TP, Liu CY, Hsu KC, Wang HC Int J Biol Macromol. 2020 Jun 3;160:903-914. doi: 10.1016/j.ijbiomac.2020.05.267. PMID:32502608<ref>PMID:32502608</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6lyv" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human gammaherpesvirus 8]] | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus]] | |||
[[Category: Ko TP]] | |||
[[Category: Liao YT]] | |||
[[Category: Wang HC]] | |||
Latest revision as of 18:05, 29 November 2023
The crystal structure of SAUGI/KSHVUDG complexThe crystal structure of SAUGI/KSHVUDG complex
Structural highlights
FunctionUNG_HHV8P Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or deamination of cytosines. Therefore may reduce deleterious uracil incorporation into the viral genome, particularly in terminally differentiated cells which lack DNA repair enzymes.[HAMAP-Rule:MF_04046] Publication Abstract from PubMedUracil-DNA glycosylases (UDGs) are conserved DNA-repair enzymes that can be found in many species, including herpesviruses. Since they play crucial roles for efficient viral DNA replication in herpesviruses, they have been considered as potential antiviral targets. In our previous work, Staphylococcus aureus SAUGI was identified as a DNA mimic protein that targets UDGs from S. aureus, human, Herpes simplex virus (HSV) and Epstein-Barr virus (EBV). Interestingly, SAUGI has the strongest inhibitory effects with EBVUDG. Here, we determined complex structures of SAUGI with EBVUDG and another gamma-herpesvirus UDG from Kaposi's sarcoma-associated herpesvirus (KSHVUDG), which SAUGI fails to effectively inhibit. Structural analysis of the SAUGI/EBVUDG complex suggests that the additional interaction between SAUGI and the leucine loop may explain why SAUGI shows the highest binding capacity with EBVUDG. In contrast, SAUGI appears to make only partial contacts with the key components responsible for the compression and stabilization of the DNA backbone in the leucine loop extension of KSHVUDG. The findings in this study provide a molecular explanation for the differential inhibitory effects and binding strengths that SAUGI has on these two UDGs, and the structural basis of the differences should be helpful in developing inhibitors that would interfere with viral DNA replication. Structural insight into the differential interactions between the DNA mimic protein SAUGI and two gamma herpesvirus uracil-DNA glycosylases.,Liao YT, Lin SJ, Ko TP, Liu CY, Hsu KC, Wang HC Int J Biol Macromol. 2020 Jun 3;160:903-914. doi: 10.1016/j.ijbiomac.2020.05.267. PMID:32502608[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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