View source for 3aca


==Crystal structure of human NUDT5 complexed with 8-oxo-dADP and manganese==
<StructureSection load='3aca' size='340' side='right'caption='[[3aca]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3aca]] is a 2 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=3ACA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ACA 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8DD:8-OXO-7,8-DIHYDRO-2-DEOXY-ADENOSINE-5-DIPHOSPHATE'>8DD</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=3aca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aca OCA], [https://pdbe.org/3aca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3aca RCSB], [https://www.ebi.ac.uk/pdbsum/3aca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3aca ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NUDT5_HUMAN NUDT5_HUMAN] Hydrolyzes with similar activities ADP-ribose ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze other nucleotide sugars with low activity.<ref>PMID:17052728</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human NUDT5 (hNUDT5) hydrolyzes various modified nucleoside diphosphates including 8-oxo-dGDP, 8-oxo-dADP and ADP-ribose (ADPR). However, the structural basis of the broad substrate specificity remains unknown. Here, we report the crystal structures of hNUDT5 complexed with 8-oxo-dGDP and 8-oxo-dADP. These structures reveal an unusually different substrate-binding mode. In particular, the positions of two phosphates (alpha and beta phosphates) of substrate in the 8-oxo-dGDP and 8-oxo-dADP complexes are completely inverted compared with those in the previously reported hNUDT5-ADPR complex structure. This result suggests that the nucleophilic substitution sites of the substrates involved in hydrolysis reactions differ despite the similarities in the chemical structures of the substrates and products. To clarify this hypothesis, we employed the isotope-labeling method and revealed that 8-oxo-dGDP is attacked by nucleophilic water at Pbeta, whereas ADPR is attacked at Palpha. This observation reveals that the broad substrate specificity of hNUDT5 is achieved by a diversity of not only substrate recognition, but also hydrolysis mechanisms and leads to a novel aspect that enzymes do not always catalyze the reaction of substrates with similar chemical structures by using the chemically equivalent reaction site.

Diverse substrate recognition and hydrolysis mechanisms of human NUDT5.,Arimori T, Tamaoki H, Nakamura T, Kamiya H, Ikemizu S, Takagi Y, Ishibashi T, Harashima H, Sekiguchi M, Yamagata Y Nucleic Acids Res. 2011 Nov 1;39(20):8972-83. Epub 2011 Jul 17. PMID:21768126<ref>PMID:21768126</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3aca" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arimori T]]
[[Category: Yamagata Y]]