2py4
From Proteopedia
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| - | [[Image:2py4.png|left|200px]] | ||
| - | + | ==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=''> | ||
| + | == Structural highlights == | ||
| + | <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='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='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='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> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [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 == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/py/2py4_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2py4 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:18519027</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2py4" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[ | + | *[[DUTPase 3D structures|DUTPase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
| - | + | [[Category: Barabas O]] | |
| - | [[Category: Barabas | + | [[Category: Nagy N]] |
| - | [[Category: Nagy | + | [[Category: Takacs E]] |
| - | [[Category: Takacs | + | [[Category: Vertessy BG]] |
| - | [[Category: Vertessy | + | |
| - | + | ||
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Current revision
Full length structure of the Mycobacterium tuberculosis dUTPase complexed with magnesium and alpha,beta-imido-dUTP.
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