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| | <StructureSection load='7aus' size='340' side='right'caption='[[7aus]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='7aus' size='340' side='right'caption='[[7aus]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7aus]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7aus]] 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=7AUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUS FirstGlance]. <br> |
| - | </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=RYT:pentadecaphosphate'>RYT</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]] 1.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7aui|7aui]], [[7auj|7auj]], [[7auk|7auk]], [[7aul|7aul]], [[7aum|7aum]], [[7aun|7aun]], [[7auo|7auo]], [[7aup|7aup]], [[7auq|7auq]], [[7aur|7aur]]</div></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=RYT:pentadecaphosphate'>RYT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDP1, YOR163W, O3575 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=7aus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aus OCA], [https://pdbe.org/7aus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aus RCSB], [https://www.ebi.ac.uk/pdbsum/7aus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aus ProSAT]</span></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=7aus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aus OCA], [https://pdbe.org/7aus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aus RCSB], [https://www.ebi.ac.uk/pdbsum/7aus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aus ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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).
| + | [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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gonzalez, B]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Marquez-Monino, M A]] | + | [[Category: Gonzalez B]] |
| - | [[Category: Ddp1]] | + | [[Category: Marquez-Monino MA]] |
| - | [[Category: Diadenosine polyphosphate]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inositol]]
| + | |
| - | [[Category: Nudix]]
| + | |
| - | [[Category: Polyphosphate]]
| + | |
| - | [[Category: Pp-insp]]
| + | |
| - | [[Category: Pyrophosphatase]]
| + | |
| Structural highlights
Function
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).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Marquez-Monino MA, Ortega-Garcia R, Shipton ML, Franco-Echevarria E, Riley AM, Sanz-Aparicio J, Potter BVL, Gonzalez B. Multiple substrate recognition by yeast diadenosine and diphosphoinositol polyphosphate phosphohydrolase through phosphate clamping. Sci Adv. 2021 Apr 23;7(17). pii: 7/17/eabf6744. doi: 10.1126/sciadv.abf6744., Print 2021 Apr. PMID:33893105 doi:http://dx.doi.org/10.1126/sciadv.abf6744
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