2oke: Difference between revisions

Latest revision as of 10:41, 30 August 2023

High Resolution Crystal Structures of Vaccinia Virus dUTPase

Structural highlights

2oke is a 3 chain structure with sequence from Vaccinia virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	CL, DUP, EDO, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[1]

[2]

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2oke]] 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=2OKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OKE 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=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2okd|2okd]], [[2okb|2okb]], [[2ol1|2ol1]], [[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=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2oke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oke OCA], [https://pdbe.org/2oke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oke RCSB], [https://www.ebi.ac.uk/pdbsum/2oke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oke ProSAT]</span></td></tr>
 </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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 38: / Line 38: @@
 [[Category: Large Structures]]
 [[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]]

2oke: Difference between revisions

Latest revision as of 10:41, 30 August 2023

High Resolution Crystal Structures of Vaccinia Virus dUTPase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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