5lqq: Difference between revisions

Latest revision as of 18:41, 18 October 2023

Structure of Autotaxin (ENPP2) with LM350

Structural highlights

5lqq 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 2.4Å
Ligands:	72P, BMA, CA, IOD, MAN, NA, NAG, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENPP2_RAT

Publication Abstract from PubMed

Autotaxin (ATX) is a secreted enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) to the bioactive lysophosphatidic acid (LPA) and choline. The ATX-LPA signalling pathway is implicated in cell survival, migration, and proliferation; thus, the inhibition of ATX is a recognized therapeutic target for a number of diseases including fibrotic diseases, cancer, and inflammation, amongst others. Many of the developed synthetic inhibitors for ATX have resembled the lipid chemotype of the native ligand; however, a small number of inhibitors have been described that deviate from this common scaffold. Herein, we report the structure-activity relationships (SAR) of a previously reported small molecule ATX inhibitor. We show through enzyme kinetics studies that analogues of this chemotype are noncompetitive inhibitors, and using a crystal structure with ATX we confirm the discrete binding mode.

Structure-activity Relationships of Small Molecule Autotaxin Inhibitors with a Discrete Binding Mode.,Miller LM, Keune WJ, Castagna D, Young LC, Duffy EL, Potjewyd F, Salgado-Polo F, Engel Garcia P, Semaan D, Pritchard JM, Perrakis A, Macdonald SJ, Jamieson C, Watson AJ J Med Chem. 2016 Dec 16. PMID:27982588^[1]

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

References

↑ Miller LM, Keune WJ, Castagna D, Young LC, Duffy EL, Potjewyd F, Salgado-Polo F, Engel Garcia P, Semaan D, Pritchard JM, Perrakis A, Macdonald SJ, Jamieson C, Watson AJ. Structure-activity Relationships of Small Molecule Autotaxin Inhibitors with a Discrete Binding Mode. J Med Chem. 2016 Dec 16. PMID:27982588 doi:https://dx.doi.org/10.1021/acs.jmedchem.6b01597

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OCA

[1] Miller LM, Keune WJ, Castagna D, Young LC, Duffy EL, Potjewyd F, Salgado-Polo F, Engel Garcia P, Semaan D, Pritchard JM, Perrakis A, Macdonald SJ, Jamieson C, Watson AJ. Structure-activity Relationships of Small Molecule Autotaxin Inhibitors with a Discrete Binding Mode. J Med Chem. 2016 Dec 16. PMID:27982588 doi:https://dx.doi.org/10.1021/acs.jmedchem.6b01597

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='5lqq' size='340' side='right'caption='[[5lqq]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5lqq]] 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=5LQQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LQQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5lqq]] 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=5LQQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LQQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=72P:3-(6-CHLORANYL-2-METHYL-1-PHENYL-INDOL-3-YL)SULFANYLBENZOIC+ACID'>72P</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.4&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=72P:3-(6-CHLORANYL-2-METHYL-1-PHENYL-INDOL-3-YL)SULFANYLBENZOIC+ACID'>72P</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5lqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lqq OCA], [https://pdbe.org/5lqq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lqq RCSB], [https://www.ebi.ac.uk/pdbsum/5lqq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lqq ProSAT]</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=5lqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lqq OCA], [http://pdbe.org/5lqq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lqq RCSB], [http://www.ebi.ac.uk/pdbsum/5lqq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lqq 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 25: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Alkylglycerophosphoethanolamine phosphodiesterase]]
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
-[[Category: Castelmur, E]]
+[[Category: Rattus norvegicus]]
-[[Category: Heidebrecht, T]]
+[[Category: Castelmur E]]
-[[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: Ectonucleotide pyrophosphatase/phosphodiesterase]]
-[[Category: Enpp2]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]
-[[Category: Lm350]]

5lqq: Difference between revisions

Latest revision as of 18:41, 18 October 2023

Structure of Autotaxin (ENPP2) with LM350

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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