7prm: Difference between revisions

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<StructureSection load='7prm' size='340' side='right'caption='[[7prm]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
<StructureSection load='7prm' size='340' side='right'caption='[[7prm]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<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>
<table><tr><td colspan='2'>[[7prm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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='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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</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='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='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>
<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 ==
== 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>
[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>
==See Also==
 
*[[Lipase 3D Structures|Lipase 3D Structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7prm" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Acylglycerol lipase]]
[[Category: Homo sapiens]]
[[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]]

Latest revision as of 10:52, 1 May 2024

CRYSTAL STRUCTURE OF HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 13CRYSTAL STRUCTURE OF HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 13

Structural highlights

7prm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.65Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

See Also

References

  1. ↑ Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell. 2010 Jan 8;140(1):49-61. doi: 10.1016/j.cell.2009.11.027. PMID:20079333 doi:10.1016/j.cell.2009.11.027

7prm, resolution 1.65Å

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