View source for 4dlc


==Crystal Structure of Trypanosoma brucei dUTPase with dUMP, MgF3- transition state analogue, and Mg2+==
<StructureSection load='4dlc' size='340' side='right'caption='[[4dlc]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dlc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DLC 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]] 1.759&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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=4dlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dlc OCA], [https://pdbe.org/4dlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dlc RCSB], [https://www.ebi.ac.uk/pdbsum/4dlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dlc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q57ZH3_TRYB2 Q57ZH3_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Tritryps Trypanosoma brucei, T. cruzi and Leishmania donovani are responsible for great morbidity and mortality in developing countries. Their dimeric dUTPases are members of the all-a NTP pyrophosphohydrolase family and represent promising drug targets due to their essential nature and markedly different structural and biochemical properties compared to the trimeric human enzyme. Here we present the structure of the T. brucei enzyme in open and closed conformations. Furthermore, we probe the reaction mechanism through the binding of transition state mimics both in solution and in the crystal. 31P-NMR and tryptophan fluorescence quenching in the presence of AlF3 and MgF3- identified which phosphate is subject to nucleophilic attack by a water molecule. The structures in complex with two transition state analogues confirm that the nucleophilic attack occurs on the b-phosphate in contrast to the a-phosphate in the trimeric enzymes. These results establish the structural basis of catalysis of these important house-keeping enzymes and has ramifications for the wider all-a NTP pyrophosphohydrolase family.

On the catalytic mechanism of dimeric dUTPases.,Hemsworth GR, Gonzalez-Pacanowska D, Wilson KS Biochem J. 2013 Sep 4. PMID:24001052<ref>PMID:24001052</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4dlc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei]]
[[Category: Gonzalez-Pacanowska D]]
[[Category: Hemsworth GR]]
[[Category: Wilson KS]]