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==Yeast Diphosphoinositol Polyphosphate Phosphohydrolase DDP1 in complex with PCP-InsP7==
<StructureSection load='7aup' size='340' side='right'caption='[[7aup]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7aup]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUP 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]] 1.85&#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=VEB:[oxidanyl-[(2~{S},3~{S},5~{R},6~{S})-2,3,4,5,6-pentaphosphonooxycyclohexyl]oxy-phosphoryl]methylphosphonic+acid'>VEB</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=7aup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aup OCA], [https://pdbe.org/7aup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aup RCSB], [https://www.ebi.ac.uk/pdbsum/7aup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aup ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DDP1_YEAST DDP1_YEAST] May eliminate potentially toxic dinucleoside polyphosphates during sporulation. Most active against diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A). Can also hydrolyze diadenosine 5',5'''-P1,P5-pentaphosphate (Ap5A), adenosine 5'-pentaphosphate, and adenosine 5'-tetraphosphate are also substrates, but not diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) or other dinucleotides, mononucleotides, nucleotide sugars, or nucleotide alcohols. Also cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate).
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== Publication Abstract from PubMed ==
The yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase DDP1 is a Nudix enzyme with pyrophosphatase activity on diphosphoinositides, dinucleotides, and polyphosphates. These substrates bind to diverse protein targets and participate in signaling and metabolism, being essential for energy and phosphate homeostasis, ATPase pump regulation, or protein phosphorylation. An exhaustive structural study of DDP1 in complex with multiple ligands related to its three diverse substrate classes is reported. This allowed full characterization of the DDP1 active site depicting the molecular basis for endowing multisubstrate abilities to a Nudix enzyme, driven by phosphate anchoring following a defined path. This study, combined with multiple enzyme variants, reveals the different substrate binding modes, preferences, and selection. Our findings expand current knowledge on this important structural superfamily with implications extending beyond inositide research. This work represents a valuable tool for inhibitor/substrate design for ScDDP1 and orthologs as potential targets to address fungal infections and other health concerns.

Multiple substrate recognition by yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase through phosphate clamping.,Marquez-Monino MA, Ortega-Garcia R, Shipton ML, Franco-Echevarria E, Riley AM, Sanz-Aparicio J, Potter BVL, Gonzalez B Sci Adv. 2021 Apr 23;7(17). pii: 7/17/eabf6744. doi: 10.1126/sciadv.abf6744., Print 2021 Apr. PMID:33893105<ref>PMID:33893105</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7aup" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Gonzalez B]]
[[Category: Marquez-Monino MA]]