5dlw: Difference between revisions

Latest revision as of 21:48, 28 June 2023

Crystal structure of Autotaxin (ENPP2) with tauroursodeoxycholic acid (TUDCA) and lysophosphatidic acid (LPA)

Structural highlights

5dlw is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	5D5, BMA, CA, GOL, IOD, MAN, NA, NAG, NKP, SCN, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENPP2_RAT

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

↑ 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:https://dx.doi.org/10.1038/ncomms11248

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OCA

[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:https://dx.doi.org/10.1038/ncomms11248

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='5dlw' size='340' side='right'caption='[[5dlw]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5dlw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DLW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DLW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5dlw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DLW FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NKP:(2R)-2-HYDROXY-3-(PHOSPHONOOXY)PROPYL+(9E)-OCTADEC-9-ENOATE'>NKP</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dlt|5dlt]], [[5dlv|5dlv]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NKP:(2R)-2-HYDROXY-3-(PHOSPHONOOXY)PROPYL+(9E)-OCTADEC-9-ENOATE'>NKP</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Enpp2, Atx, Npps2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=5dlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlw OCA], [https://pdbe.org/5dlw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dlw RCSB], [https://www.ebi.ac.uk/pdbsum/5dlw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlw ProSAT]</span></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://proteopedia.org/fgij/fg.htm?mol=5dlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlw OCA], [http://pdbe.org/5dlw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dlw RCSB], [http://www.ebi.ac.uk/pdbsum/5dlw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlw ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/ENPP2_RAT ENPP2_RAT]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Alkylglycerophosphoethanolamine phosphodiesterase]]
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
-[[Category: Heidebrecht, T]]
+[[Category: Rattus norvegicus]]
-[[Category: Joosten, R P]]
+[[Category: Heidebrecht T]]
-[[Category: Keune, W J]]
+[[Category: Joosten RP]]
-[[Category: Perrakis, A]]
+[[Category: Keune WJ]]
-[[Category: Autotaxin]]
+[[Category: Perrakis A]]
-[[Category: Bile salt]]
-[[Category: Enpp2]]
-[[Category: Hydrolase]]
-[[Category: Lpa]]
-[[Category: Steroid]]
-[[Category: Tudca]]

5dlw: Difference between revisions

Latest revision as of 21:48, 28 June 2023

Crystal structure of Autotaxin (ENPP2) with tauroursodeoxycholic acid (TUDCA) and lysophosphatidic acid (LPA)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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