View source for 6pcl


==Crystal structure of human diphosphoinositol polyphosphate phosphohydrolase 1 in complex with 5-IP7==
<StructureSection load='6pcl' size='340' side='right'caption='[[6pcl]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pcl]] is a 1 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=6PCL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PCL 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]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=I7P:(1R,2R,3S,4S,5R,6S)-2,3,4,5,6-PENTAKIS(PHOSPHONOOXY)CYCLOHEXYL+TRIHYDROGEN+DIPHOSPHATE'>I7P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=6pcl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pcl OCA], [https://pdbe.org/6pcl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pcl RCSB], [https://www.ebi.ac.uk/pdbsum/6pcl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pcl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NUDT3_HUMAN NUDT3_HUMAN] Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate.<ref>PMID:9822604</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inositol diphosphates (PP-IPs), also known as inositol pyrophosphates, are high-energy cellular signaling codes involved in nutrient and regulatory responses. We report that the evolutionarily conserved gene product, Vip1, possesses autonomous kinase and pyrophosphatase domains capable of synthesis and destruction of D-1 PP-IPs. Our studies provide atomic-resolution structures of the PP-IP products and unequivocally define that the Vip1 gene product is a highly selective 1-kinase and 1-pyrophosphatase enzyme whose activities arise through distinct active sites. Kinetic analyses of kinase and pyrophosphatase parameters are consistent with Vip1 evolving to modulate levels of 1-IP7 and 1,5-IP8 Individual perturbations in kinase and pyrophosphatase activities in cells result in differential effects on vacuolar morphology and osmotic responses. Analogous to the dual-functional key energy metabolism regulator, phosphofructokinase 2, Vip1 is a kinase and pyrophosphatase switch whose 1-PP-IP products play an important role in a cellular adaptation.

Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling.,Dollins DE, Bai W, Fridy PC, Otto JC, Neubauer JL, Gattis SG, Mehta KPM, York JD Proc Natl Acad Sci U S A. 2020 Apr 17. pii: 1908875117. doi:, 10.1073/pnas.1908875117. PMID:32303658<ref>PMID:32303658</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pcl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dollins DE]]
[[Category: Dong J]]
[[Category: Neubauer J]]
[[Category: York JD]]