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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2okd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OKD FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2okd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OKD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2okb|2okb]], [[1q5u|1q5u]], [[2ol1|2ol1]], [[2oke|2oke]], [[2ol0|2ol0]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10245 Vaccinia virus])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=2okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2okd OCA], [https://pdbe.org/2okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2okd RCSB], [https://www.ebi.ac.uk/pdbsum/2okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2okd 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=2okd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2okd OCA], [https://pdbe.org/2okd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2okd RCSB], [https://www.ebi.ac.uk/pdbsum/2okd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2okd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DUT_VACCW DUT_VACCW] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:18321387</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Vaccinia virus]] | | [[Category: Vaccinia virus]] |
| - | [[Category: DUTP diphosphatase]]
| + | [[Category: Chattopadhyay D]] |
| - | [[Category: Chattopadhyay, D]] | + | [[Category: Schormann N]] |
| - | [[Category: Schormann, N]] | + | |
| - | [[Category: Dutpase-like]]
| + | |
| - | [[Category: Fold]]
| + | |
| - | [[Category: Forms tight trimer through an additional beta-sheet in each subunit]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Jelly-roll]]
| + | |
| - | [[Category: Subunit beta-sheets are orthogonally packed around the three-fold axis]]
| + | |
| - | [[Category: Superfamily]]
| + | |
| Structural highlights
Function
DUT_VACCW This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate in the presence of Mg(2+) ions. The enzyme plays multiple cellular roles by maintaining a low dUTP:dTTP ratio and by synthesizing the substrate for thymidylate synthase in the biosynthesis of dTTP. Although dUTPase is an essential enzyme and has been established as a valid target for drug design, the high degree of homology of vaccinia virus dUTPase to the human enzyme makes the identification of selective inhibitors difficult. The crystal structure of vaccinia virus dUTPase has been solved and the active site has been mapped by crystallographic analysis of the apo enzyme and of complexes with the substrate-analog dUMPNPP, with the product dUMP and with dUDP, which acts as an inhibitor. Analyses of these structures reveal subtle differences between the viral and human enzymes. In particular, the much larger size of the central channel at the trimer interface suggests new possibilities for structure-based drug design. Vaccinia virus is a prototype of the poxviruses.
Structures of vaccinia virus dUTPase and its nucleotide complexes.,Samal A, Schormann N, Cook WJ, DeLucas LJ, Chattopadhyay D Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):571-80. Epub 2007, Apr 21. PMID:17452782[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Prichard MN, Kern ER, Quenelle DC, Keith KA, Moyer RW, Turner PC. Vaccinia virus lacking the deoxyuridine triphosphatase gene (F2L) replicates well in vitro and in vivo, but is hypersensitive to the antiviral drug (N)-methanocarbathymidine. Virol J. 2008 Mar 5;5:39. PMID:18321387 doi:10.1186/1743-422X-5-39
- ↑ Samal A, Schormann N, Cook WJ, DeLucas LJ, Chattopadhyay D. Structures of vaccinia virus dUTPase and its nucleotide complexes. Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):571-80. Epub 2007, Apr 21. PMID:17452782 doi:10.1107/S0907444907007871
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