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{{STRUCTURE_3nkr|  PDB=3nkr  |  SCENE=  }}
===Crystal structure of mouse autotaxin in complex with 22:6-LPA===
{{ABSTRACT_PUBMED_21240269}}


==Disease==
==Crystal structure of mouse autotaxin in complex with 22:6-LPA==
[[http://www.uniprot.org/uniprot/ENPP2_MOUSE ENPP2_MOUSE]] Note=May contribute to obesity.  
<StructureSection load='3nkr' size='340' side='right'caption='[[3nkr]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3nkr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NKR 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]] 1.704&#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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NKR:(2R)-2-HYDROXY-3-(PHOSPHONOOXY)PROPYL+(4Z,7E,10E,13Z,16Z,19Z)-DOCOSA-4,7,10,13,16,19-HEXAENOATE'>NKR</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=3nkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nkr OCA], [https://pdbe.org/3nkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nkr RCSB], [https://www.ebi.ac.uk/pdbsum/3nkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nkr ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ENPP2_MOUSE ENPP2_MOUSE] Note=May contribute to obesity.
== Function ==
[https://www.uniprot.org/uniprot/ENPP2_MOUSE ENPP2_MOUSE] Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor.<ref>PMID:15700135</ref> <ref>PMID:17208043</ref> <ref>PMID:21240269</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Autotaxin (ATX, also known as Enpp2) is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine to generate lysophosphatidic acid (LPA), a lipid mediator that activates G protein-coupled receptors to evoke various cellular responses. Here, we report the crystal structures of mouse ATX alone and in complex with LPAs with different acyl-chain lengths and saturations. These structures reveal that the multidomain architecture helps to maintain the structural rigidity of the lipid-binding pocket, which accommodates the respective LPA molecules in distinct conformations. They indicate that a loop region in the catalytic domain is a major determinant for the substrate specificity of the Enpp family enzymes. Furthermore, along with biochemical and biological data, these structures suggest that the produced LPAs are delivered from the active site to cognate G protein-coupled receptors through a hydrophobic channel.


==Function==
Crystal structure of autotaxin and insight into GPCR activation by lipid mediators.,Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O Nat Struct Mol Biol. 2011 Feb;18(2):205-12. doi: 10.1038/nsmb.1998. Epub 2011 Jan, 16. PMID:21240269<ref>PMID:21240269</ref>
[[http://www.uniprot.org/uniprot/ENPP2_MOUSE ENPP2_MOUSE]] Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor.<ref>PMID:15700135</ref> <ref>PMID:17208043</ref> <ref>PMID:21240269</ref>


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[3nkr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NKR OCA].
</div>
<div class="pdbe-citations 3nkr" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
<ref group="xtra">PMID:021240269</ref><references group="xtra"/><references/>
*[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]]
[[Category: Alkylglycerophosphoethanolamine phosphodiesterase]]
== References ==
[[Category: Lk3 transgenic mice]]
<references/>
[[Category: Aoki, J.]]
__TOC__
[[Category: Ishitani, R.]]
</StructureSection>
[[Category: Mihara, E.]]
[[Category: Large Structures]]
[[Category: Nishimasu, H.]]
[[Category: Mus musculus]]
[[Category: Nureki, O.]]
[[Category: Aoki J]]
[[Category: Takagi, J.]]
[[Category: Ishitani R]]
[[Category: Autotaxin]]
[[Category: Mihara E]]
[[Category: Enpp2]]
[[Category: Nishimasu H]]
[[Category: Hydrolase]]
[[Category: Nureki O]]
[[Category: Lysophosphatidic acid]]
[[Category: Takagi J]]
[[Category: Lysophospholipase d]]

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