View source for 4lr2


==Crystal Structure of Human ENPP4 (apo)==
<StructureSection load='4lr2' size='340' side='right'caption='[[4lr2]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4lr2]] 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=4LR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LR2 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4lr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lr2 OCA], [https://pdbe.org/4lr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lr2 RCSB], [https://www.ebi.ac.uk/pdbsum/4lr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lr2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ENPP4_HUMAN ENPP4_HUMAN] Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors.<ref>PMID:22995898</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
NPP4 is a type I extracellular membrane protein on brain vascular endothelium inducing platelet aggregation via the hydrolysis of Ap3A, whereas NPP1 is a type II extracellular membrane protein principally present on the surface of chondrocytes that regulates tissue mineralization. To understand the metabolism of purinergic signals resulting in the physiologic activities of the two enzymes, we report the high resolution crystal structure of human NPP4 and explore the molecular basis of its substrate specificity with NPP1. Both enzymes cleave Ap3A, but only NPP1 can hydrolyze ATP. Comparative structural analysis reveals a tripartite lysine claw in NPP1 that stabilizes the terminal phosphate of ATP, whereas the corresponding region of NPP4 contains features that hinder this binding orientation, thereby inhibiting ATP hydrolysis. Furthermore, we show that NPP1 is unable to induce platelet aggregation at physiologic concentrations reported in human blood, but it could stimulate platelet aggregation if localized at low nanomolar concentrations on vascular endothelium. The combined studies expand our understanding of NPP1 and NPP4 substrate specificity and range and provide a rational mechanism by which polymorphisms in NPP1 confer stroke resistance.

Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke.,Albright RA, Ornstein DL, Cao W, Chang WC, Robert D, Tehan M, Hoyer D, Liu L, Stabach P, Yang G, De La Cruz EM, Braddock DT J Biol Chem. 2014 Feb 7;289(6):3294-306. doi: 10.1074/jbc.M113.505867. Epub 2013 , Dec 12. PMID:24338010<ref>PMID:24338010</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4lr2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Albright RA]]
[[Category: Braddock DT]]