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| | <StructureSection load='6lj3' size='340' side='right'caption='[[6lj3]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6lj3' size='340' side='right'caption='[[6lj3]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6lj3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Asf Asf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LJ3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lj3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/African_swine_fever_virus African swine fever virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LJ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LJ3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E165R CDS, E165R, ASFV-Georgia_4-154, ASFV_Kyiv_2016_131_00207 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10497 ASF])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=6lj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lj3 OCA], [https://pdbe.org/6lj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lj3 RCSB], [https://www.ebi.ac.uk/pdbsum/6lj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lj3 ProSAT]</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=6lj3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lj3 OCA], [https://pdbe.org/6lj3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lj3 RCSB], [https://www.ebi.ac.uk/pdbsum/6lj3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lj3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DUTP_ASFB7 DUTP_ASFB7] The viral dUTPase may play a role in lowering the dUTP concentration in natural infections to minimize misincorporation of deoxyuridine into the viral DNA and ensure the fidelity of genome replication.<ref>PMID:10515998</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Asf]] | + | [[Category: African swine fever virus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liang, R]] | + | [[Category: Liang R]] |
| - | [[Category: Peng, G Q]] | + | [[Category: Peng GQ]] |
| - | [[Category: Adut]]
| + | |
| - | [[Category: Asfv]]
| + | |
| - | [[Category: Dutpase]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
DUTP_ASFB7 The viral dUTPase may play a role in lowering the dUTP concentration in natural infections to minimize misincorporation of deoxyuridine into the viral DNA and ensure the fidelity of genome replication.[1]
Publication Abstract from PubMed
African swine fever, caused by the African swine fever virus (ASFV), is among the most significant swine diseases. There are currently no effective treatments against ASFV. ASFV contains a gene encoding a dUTPase (E165R), which is required for viral replication in swine macrophages, making it an attractive target for inhibitor development. However, the full structural details of the ASFV dUTPase and those of the comparable swine enzyme are not available, limiting further insights. Herein, we determine the crystal structures of ASFV dUTPase and swine dUTPase in both their ligand-free and ligand-bound forms. We observe that the swine enzyme employs a classical dUTPase architecture made up of three-subunit active sites, whereas the ASFV enzyme employs a novel two-subunit active site. We then performed a comparative analysis of all dUTPase structures uploaded in PDB, which showed classic and non-classical types were mainly determined by the C-terminal beta-strand orientation, and the difference was mainly related to the four amino acids behind motif IV. Thus, our study not only explains the reason for the structural diversity of dUTPase but also reveals how to predict dUTPase type, which may have implications for the dUTPase family. Finally, we tested two dUTPase inhibitors developed for the Plasmodium falciparum dUTPase against the swine and ASFV enzymes. One of these compounds inhibited the ASFV dUTPase at low micromolar concentrations (Kd =15.6muM) and with some selectivity (~2x) over swine dUTPase. In conclusion, our study expands our understanding of the dUTPase family and may aid in the development of specific ASFV inhibitors.
Structural comparisons of host and African swine fever virus dUTPases reveal new clues for inhibitor development.,Liang R, Wang G, Zhang D, Ye G, Li M, Shi Y, Shi J, Chen H, Peng G J Biol Chem. 2020 Nov 2. pii: RA120.014005. doi: 10.1074/jbc.RA120.014005. PMID:33139328[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oliveros M, García-Escudero R, Alejo A, Viñuela E, Salas ML, Salas J. African swine fever virus dUTPase is a highly specific enzyme required for efficient replication in swine macrophages. J Virol. 1999 Nov;73(11):8934-43. PMID:10515998 doi:10.1128/JVI.73.11.8934-8943.1999
- ↑ Liang R, Wang G, Zhang D, Ye G, Li M, Shi Y, Shi J, Chen H, Peng G. Structural comparisons of host and African swine fever virus dUTPases reveal new clues for inhibitor development. J Biol Chem. 2020 Nov 2. pii: RA120.014005. doi: 10.1074/jbc.RA120.014005. PMID:33139328 doi:http://dx.doi.org/10.1074/jbc.RA120.014005
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