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| | ==Full length structure of the Mycobacterium tuberculosis dUTPase complexed with magnesium and alpha,beta-imido-dUTP.== | | ==Full length structure of the Mycobacterium tuberculosis dUTPase complexed with magnesium and alpha,beta-imido-dUTP.== |
| - | <StructureSection load='2py4' size='340' side='right' caption='[[2py4]], [[Resolution|resolution]] 1.49Å' scene=''> | + | <StructureSection load='2py4' size='340' side='right'caption='[[2py4]], [[Resolution|resolution]] 1.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2py4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PY4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2py4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PY4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.49Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mq7|1mq7]], [[1six|1six]]</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>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dut ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=2py4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2py4 OCA], [https://pdbe.org/2py4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2py4 RCSB], [https://www.ebi.ac.uk/pdbsum/2py4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2py4 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2py4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2py4 OCA], [http://pdbe.org/2py4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2py4 RCSB], [http://www.ebi.ac.uk/pdbsum/2py4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2py4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DUT_MYCTU DUT_MYCTU]] 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.[HAMAP-Rule:MF_00116] | + | [https://www.uniprot.org/uniprot/DUT_MYCTU DUT_MYCTU] 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.[HAMAP-Rule:MF_00116] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Deoxyuridine 5'-triphosphate nucleotidohydrolase|Deoxyuridine 5'-triphosphate nucleotidohydrolase]] | + | *[[DUTPase 3D structures|DUTPase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DUTP diphosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Barabas, O]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Nagy, N]] | + | [[Category: Barabas O]] |
| - | [[Category: Takacs, E]] | + | [[Category: Nagy N]] |
| - | [[Category: Vertessy, B G]] | + | [[Category: Takacs E]] |
| - | [[Category: Enzyme-ligand complex]]
| + | [[Category: Vertessy BG]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Jelly-roll]]
| + | |
| Structural highlights
Function
DUT_MYCTU 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.[HAMAP-Rule:MF_00116]
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
dUTPases are essential to eliminate dUTP for DNA integrity and provide dUMP for thymidylate biosynthesis. Mycobacterium tuberculosis apparently lacks any other thymidylate biosynthesis pathway, therefore dUTPase is a promising antituberculotic drug target. Crystal structure of the mycobacterial enzyme in complex with the isosteric substrate analog, alpha,beta-imido-dUTP and Mg(2+) at 1.5A resolution was determined that visualizes the full-length C-terminus, previously not localized. Interactions of a conserved motif important in catalysis, the Mycobacterium-specific five-residue-loop insert and C-terminal tetrapeptide could now be described in detail. Stacking of C-terminal histidine upon the uracil moiety prompted replacement with tryptophan. The resulting sensitive fluorescent sensor enables fast screening for binding of potential inhibitors to the active site. K(d) for alpha,beta-imido-dUTP binding to mycobacterial dUTPase is determined to be 10-fold less than for human dUTPase, which is to be considered in drug optimization. A robust continuous activity assay for kinetic screening is proposed.
Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor.,Varga B, Barabas O, Takacs E, Nagy N, Nagy P, Vertessy BG Biochem Biophys Res Commun. 2008 Aug 15;373(1):8-13. Epub 2008 Jun 2. PMID:18519027[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Varga B, Barabas O, Takacs E, Nagy N, Nagy P, Vertessy BG. Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor. Biochem Biophys Res Commun. 2008 Aug 15;373(1):8-13. Epub 2008 Jun 2. PMID:18519027 doi:10.1016/j.bbrc.2008.05.130
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