View source for 6wet


==Crystal structures of human E-NPP 1: apo==
<StructureSection load='6wet' size='340' side='right'caption='[[6wet]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wet]] 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=6WET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WET 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6wet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wet OCA], [https://pdbe.org/6wet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wet RCSB], [https://www.ebi.ac.uk/pdbsum/6wet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wet ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ENPP1_HUMAN ENPP1_HUMAN] Defects in ENPP1 are a cause of increased susceptibility for ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:[https://omim.org/entry/602475 602475]. OPLL is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups.<ref>PMID:10453738</ref>   Defects in ENPP1 are the cause of arterial calcification of infancy, generalized, type 1 (GACI1) [MIM:[https://omim.org/entry/208000 208000]. A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure.<ref>PMID:12881724</ref> <ref>PMID:15940697</ref> <ref>PMID:15605415</ref> <ref>PMID:22209248</ref>   Defects in ENPP1 are associated with obesity, glucose intolerance, and type II diabetes non-insulin dependent (NIDDM) [MIM:[https://omim.org/entry/125853 125853].<ref>PMID:16186408</ref>   Defects in ENPP1 are the cause of rickets hypophosphatemic autosomal recessive type 2 (ARHR2) [MIM:[https://omim.org/entry/613312 613312]. ARHR2 is a hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities.<ref>PMID:20137773</ref> <ref>PMID:20137772</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ENPP1_HUMAN ENPP1_HUMAN] Involved primarily in ATP hydrolysis at the plasma membrane. Plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. In vitro, has a broad specificity, hydrolyzing other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates with release of pyrophosphate and diadenosine polyphosphates, and also 3',5'-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Appears to modulate insulin sensitivity.<ref>PMID:10615944</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cancer is one of the leading causes of mortality in humans, and recent work has focused on the area of immuno-oncology, in which the immune system is used to specifically target cancerous cells. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an emerging therapeutic target in human cancers owing to its role in degrading cyclic GMP-AMP (cGAMP), an agonist of the stimulator of interferon genes (STING). The available structures of ENPP1 are of the mouse enzyme, and no structures are available with anything other than native nucleotides. Here, the first X-ray crystal structures of the human ENPP1 enzyme in an apo form, with bound nucleotides and with two known inhibitors are presented. The availability of these structures and a robust crystallization system will allow the development of structure-based drug-design campaigns against this attractive cancer therapeutic target.

Crystal structures of human ENPP1 in apo and bound forms.,Dennis ML, Newman J, Dolezal O, Hattarki M, Surjadi RN, Nuttall SD, Pham T, Nebl T, Camerino M, Khoo PS, Monahan BJ, Peat TS Acta Crystallogr D Struct Biol. 2020 Sep 1;76(Pt 9):889-898. doi:, 10.1107/S2059798320010505. Epub 2020 Aug 17. PMID:32876064<ref>PMID:32876064</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 6wet" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Dennis M]]
[[Category: Newman J]]
[[Category: Peat TS]]