5zun
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human monoacylglycerol lipase in complex with compound 3l== | |
| + | <StructureSection load='5zun' size='340' side='right' caption='[[5zun]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5zun]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZUN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZUN FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JX:(4R)-1-(2-chloro[1,1-biphenyl]-3-yl)-4-[4-(1,3-thiazole-2-carbonyl)piperazin-1-yl]pyrrolidin-2-one'>9JX</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acylglycerol_lipase Acylglycerol lipase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zun FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zun OCA], [http://pdbe.org/5zun PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zun RCSB], [http://www.ebi.ac.uk/pdbsum/5zun PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zun ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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 a major serine hydrolase that hydrolyzes 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain. Because 2-AG and AA are endogenous biologically active ligands in the brain, inhibition of MAGL is an attractive therapeutic target for CNS disorders, particularly neurodegenerative diseases. In this study, we report the structure-based drug design of novel piperazinyl pyrrolidin-2-ones starting from our hit compounds 2a and 2b. By enhancing the interaction of the piperazinyl pyrrolidin-2-one core and its substituents with the MAGL enzyme via design modifications, we identified a potent and reversible MAGL inhibitor, compound (R)-3t. Oral administration of compound (R)-3t to mice decreased AA levels and elevated 2-AG levels in the brain. | ||
| - | + | Design, synthesis, and evaluation of piperazinyl pyrrolidin-2-ones as a novel series of reversible monoacylglycerol lipase inhibitors.,Aida J, Fushimi M, Kusumoto T, Sugiyama H, Arimura N, Ikeda S, Sasaki M, Sogabe S, Aoyama K, Koike T J Med Chem. 2018 Sep 25. doi: 10.1021/acs.jmedchem.8b00824. PMID:30251836<ref>PMID:30251836</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5zun" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Acylglycerol lipase]] | ||
[[Category: Lane, W]] | [[Category: Lane, W]] | ||
| - | [[Category: | + | [[Category: Snell, G]] |
[[Category: Sogabe, S]] | [[Category: Sogabe, S]] | ||
| + | [[Category: Zama, Y]] | ||
| + | [[Category: Hydrolase-inhibitor complex]] | ||
| + | [[Category: Monoacylglycerol lipase]] | ||
Revision as of 07:52, 17 October 2018
Crystal structure of human monoacylglycerol lipase in complex with compound 3l
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