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| | <StructureSection load='2hqu' size='340' side='right'caption='[[2hqu]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2hqu' size='340' side='right'caption='[[2hqu]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2hqu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HQU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2hqu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HQU 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=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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUTN ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=MG:MAGNESIUM+ION'>MG</scene></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=2hqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hqu OCA], [https://pdbe.org/2hqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hqu RCSB], [https://www.ebi.ac.uk/pdbsum/2hqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hqu 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=2hqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hqu OCA], [https://pdbe.org/2hqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hqu RCSB], [https://www.ebi.ac.uk/pdbsum/2hqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hqu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN]] 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:8805593</ref>
| + | [https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN] 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:8805593</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: DUTP diphosphatase]]
| + | [[Category: Barabas O]] |
| - | [[Category: Barabas, O]] | + | [[Category: Varga B]] |
| - | [[Category: Varga, B]] | + | [[Category: Vertessy BG]] |
| - | [[Category: Vertessy, B G]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Jelly-roll]]
| + | |
| - | [[Category: Protein-substrate analogue ligand complex]]
| + | |
| Structural highlights
Function
DUT_HUMAN 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
Human dUTPase, essential for DNA integrity, is an important survival factor for cancer cells. We determined the crystal structure of the enzyme:alpha,beta-imino-dUTP:Mg complex and performed equilibrium binding experiments in solution. Ordering of the C-terminus upon the active site induces close juxtaposition of the incoming nucleophile attacker water oxygen and the alpha-phosphorus of the substrate, decreasing their distance below the van der Waals limit. Complex interactions of the C-terminus with both substrate and product were observed via a specifically designed tryptophan sensor, suitable for further detailed kinetic and ligand binding studies. Results explain the key functional role of the C-terminus.
Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase.,Varga B, Barabas O, Kovari J, Toth J, Hunyadi-Gulyas E, Klement E, Medzihradszky KF, Tolgyesi F, Fidy J, Vertessy BG FEBS Lett. 2007 Oct 2;581(24):4783-8. Epub 2007 Sep 12. PMID:17880943[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mol CD, Harris JM, McIntosh EM, Tainer JA. Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits. Structure. 1996 Sep 15;4(9):1077-92. PMID:8805593
- ↑ Varga B, Barabas O, Kovari J, Toth J, Hunyadi-Gulyas E, Klement E, Medzihradszky KF, Tolgyesi F, Fidy J, Vertessy BG. Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase. FEBS Lett. 2007 Oct 2;581(24):4783-8. Epub 2007 Sep 12. PMID:17880943 doi:10.1016/j.febslet.2007.09.005
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