7prm
From Proteopedia
(Difference between revisions)
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==CRYSTAL STRUCTURE OF HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 13== | ==CRYSTAL STRUCTURE OF HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 13== | ||
| - | <StructureSection load='7prm' size='340' side='right'caption='[[7prm]]' scene=''> | + | <StructureSection load='7prm' size='340' side='right'caption='[[7prm]], [[Resolution|resolution]] 1.65Å' 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=7PRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PRM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7prm]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PRM 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=7prm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prm OCA], [https://pdbe.org/7prm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prm RCSB], [https://www.ebi.ac.uk/pdbsum/7prm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prm ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=81I:(4~{R})-1-[4-(4-fluorophenyl)phenyl]-4-[4-(furan-2-ylcarbonyl)piperazin-1-yl]pyrrolidin-2-one'>81I</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acylglycerol_lipase Acylglycerol lipase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.23 3.1.1.23] </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=7prm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7prm OCA], [https://pdbe.org/7prm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7prm RCSB], [https://www.ebi.ac.uk/pdbsum/7prm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7prm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/MGLL_HUMAN MGLL_HUMAN]] Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.<ref>PMID:20079333</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Monoacylglycerol lipase (MAGL) is one of the key enzymes in the endocannabinoid system. Inhibition of MAGL has been proposed as an attractive approach for the treatment of various diseases. In this study, we designed and successfully synthesized two series of piperazinyl pyrrolidin-2-one derivatives as novel reversible MAGL inhibitors. (R)-[(18)F]13 was identified through the preliminary evaluation of two carbon-11-labeled racemic structures [(11)C]11 and [(11)C]16. In dynamic positron-emission tomography (PET) scans, (R)-[(18)F]13 showed a heterogeneous distribution and matched the MAGL expression pattern in the mouse brain. High brain uptake and brain-to-blood ratio were achieved by (R)-[(18)F]13 in comparison with previously reported reversible MAGL PET radiotracers. Target occupancy studies with a therapeutic MAGL inhibitor revealed a dose-dependent reduction of (R)-[(18)F]13 accumulation in the mouse brain. These findings indicate that (R)-[(18)F]13 ([(18)F]YH149) is a highly promising PET probe for visualizing MAGL non-invasively in vivo and holds great potential to support drug development. | ||
| + | |||
| + | Development of High Brain-Penetrant and Reversible Monoacylglycerol Lipase PET Tracers for Neuroimaging.,He Y, Schild M, Grether U, Benz J, Leibrock L, Heer D, Topp A, Collin L, Kuhn B, Wittwer M, Keller C, Gobbi LC, Schibli R, Mu L J Med Chem. 2022 Feb 10;65(3):2191-2207. doi: 10.1021/acs.jmedchem.1c01706. Epub , 2022 Jan 28. PMID:35089028<ref>PMID:35089028</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7prm" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Acylglycerol lipase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Benz J]] | + | [[Category: Benz, J]] |
| - | [[Category: Collin L]] | + | [[Category: Collin, L]] |
| - | [[Category: Gobbi L]] | + | [[Category: Gobbi, L]] |
| - | [[Category: Grether U]] | + | [[Category: Grether, U]] |
| - | [[Category: Heer D]] | + | [[Category: Heer, D]] |
| - | [[Category: Kuhn B]] | + | [[Category: Kuhn, B]] |
| - | [[Category: Leibrock L]] | + | [[Category: Leibrock, L]] |
| - | [[Category: Wittwer M]] | + | [[Category: Wittwer, M]] |
| + | [[Category: Alpha/beta hydrolase]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Serine esterase]] | ||
Revision as of 08:42, 23 February 2022
CRYSTAL STRUCTURE OF HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 13
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