5dlv: Difference between revisions

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'''Unreleased structure'''


The entry 5dlv is ON HOLD  until Paper Publication
==Crystal structure of Autotaxin (ENPP2) with tauroursodeoxycholic acid (TUDCA)==
<StructureSection load='5dlv' size='340' side='right' caption='[[5dlv]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5dlv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DLV FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5D5:2-{[(3ALPHA,5BETA,7ALPHA,8ALPHA,14BETA,17ALPHA)-3,7-DIHYDROXY-24-OXOCHOLAN-24-YL]AMINO}ETHANESULFONIC+ACID'>5D5</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dlt|5dlt]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alkylglycerophosphoethanolamine_phosphodiesterase Alkylglycerophosphoethanolamine phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.39 3.1.4.39] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5dlv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlv OCA], [http://pdbe.org/5dlv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dlv RCSB], [http://www.ebi.ac.uk/pdbsum/5dlv PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7alpha-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs.


Authors: Keune, W.J., Heidebrecht, T., von Castelmur, E., Joosten, R.P., Perrakis, A.
Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.,Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A Nat Commun. 2016 Apr 14;7:11248. doi: 10.1038/ncomms11248. PMID:27075612<ref>PMID:27075612</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 5dlv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Alkylglycerophosphoethanolamine phosphodiesterase]]
[[Category: Castelmur, E von]]
[[Category: Heidebrecht, T]]
[[Category: Heidebrecht, T]]
[[Category: Joosten, R.P]]
[[Category: Joosten, R P]]
[[Category: Keune, W J]]
[[Category: Perrakis, A]]
[[Category: Perrakis, A]]
[[Category: Keune, W.J]]
[[Category: Autotaxin]]
[[Category: Von Castelmur, E]]
[[Category: Bile salt]]
[[Category: Enpp2]]
[[Category: Hydrolase]]
[[Category: Lpa]]
[[Category: Steroid]]
[[Category: Tudca]]

Revision as of 22:33, 10 May 2016

Crystal structure of Autotaxin (ENPP2) with tauroursodeoxycholic acid (TUDCA)Crystal structure of Autotaxin (ENPP2) with tauroursodeoxycholic acid (TUDCA)

Structural highlights

5dlv is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , , , , , , ,
Activity:Alkylglycerophosphoethanolamine phosphodiesterase, with EC number 3.1.4.39
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Publication Abstract from PubMed

Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic groove, a hydrophobic lipid-binding pocket and a tunnel of unclear function. We present crystal structures of rat ATX bound to 7alpha-hydroxycholesterol and the bile salt tauroursodeoxycholate (TUDCA), showing how the tunnel selectively binds steroids. A structure of ATX simultaneously harbouring TUDCA in the tunnel and LPA in the pocket, together with kinetic analysis, reveals that bile salts act as partial non-competitive inhibitors of ATX, thereby attenuating LPA receptor activation. This unexpected interplay between ATX-LPA signalling and select steroids, notably natural bile salts, provides a molecular basis for the emerging association of ATX with disorders associated with increased circulating levels of bile salts. Furthermore, our findings suggest potential clinical implications in the use of steroid drugs.

Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.,Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A Nat Commun. 2016 Apr 14;7:11248. doi: 10.1038/ncomms11248. PMID:27075612[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Keune WJ, Hausmann J, Bolier R, Tolenaars D, Kremer A, Heidebrecht T, Joosten RP, Sunkara M, Morris AJ, Matas-Rico E, Moolenaar WH, Oude Elferink RP, Perrakis A. Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling. Nat Commun. 2016 Apr 14;7:11248. doi: 10.1038/ncomms11248. PMID:27075612 doi:http://dx.doi.org/10.1038/ncomms11248

5dlv, resolution 2.00Å

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OCA
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