7mfh
From Proteopedia
(Difference between revisions)
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==Crystal structure of BIO-32546 bound mouse Autotaxin== | ==Crystal structure of BIO-32546 bound mouse Autotaxin== | ||
| - | <StructureSection load='7mfh' size='340' side='right'caption='[[7mfh]]' scene=''> | + | <StructureSection load='7mfh' size='340' side='right'caption='[[7mfh]], [[Resolution|resolution]] 2.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MFH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7mfh]] 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=7MFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MFH FirstGlance]. <br> |
| - | </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=7mfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mfh OCA], [https://pdbe.org/7mfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mfh RCSB], [https://www.ebi.ac.uk/pdbsum/7mfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mfh ProSAT]</span></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]] 2.3Å</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=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZF7:(1R,3S,5S)-8-{(1S)-1-[8-(trifluoromethyl)-7-{[(1s,4R)-4-(trifluoromethyl)cyclohexyl]oxy}naphthalen-2-yl]ethyl}-8-azabicyclo[3.2.1]octane-3-carboxylic+acid'>ZF7</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=7mfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mfh OCA], [https://pdbe.org/7mfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mfh RCSB], [https://www.ebi.ac.uk/pdbsum/7mfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mfh ProSAT]</span></td></tr> | ||
</table> | </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) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy. | ||
| + | |||
| + | Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546.,Ma B, Zhang L, Sun L, Xin Z, Kumaravel G, Marcotte D, Chodaparambil JV, Wang Q, Wehr A, Jing J, Hong VS, Wang T, Huang C, Shao Z, Mi S ACS Med Chem Lett. 2021 Jun 14;12(7):1124-1129. doi:, 10.1021/acsmedchemlett.1c00211. eCollection 2021 Jul 8. PMID:34267882<ref>PMID:34267882</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7mfh" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
[[Category: Chodaparambil JV]] | [[Category: Chodaparambil JV]] | ||
Revision as of 16:10, 18 October 2023
Crystal structure of BIO-32546 bound mouse Autotaxin
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