8ptr - Revision history

OCA at 09:50, 17 October 2024

2024-10-17T09:50:21Z

← Older revision		Revision as of 09:50, 17 October 2024
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	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ptr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ptr OCA], [https://pdbe.org/8ptr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ptr RCSB], [https://www.ebi.ac.uk/pdbsum/8ptr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ptr 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=8ptr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ptr OCA], [https://pdbe.org/8ptr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ptr RCSB], [https://www.ebi.ac.uk/pdbsum/8ptr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ptr ProSAT]</span></td></tr>
	</table>		</table>
	== ~~Function~~ ==		<div style="background-color:#fffaf0;">
	~~[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>		== Publication Abstract from PubMed ==
			New potent, selective monoacylglycerol lipase (MAGL) inhibitors based on the azetidin-2-one scaffold ((+/-)-5a-v, (+/-)-6a-j, and (+/-)-7a-d) were developed as irreversible ligands, as demonstrated by enzymatic and crystallographic studies for (+/-)-5d, (+/-)-5l, and (+/-)-5r. X-ray analyses combined with extensive computational studies allowed us to clarify the binding mode of the compounds. 5v was identified as selective for MAGL when compared with other serine hydrolases. Solubility, in vitro metabolic stability, cytotoxicity, and absence of mutagenicity were determined for selected analogues. The most promising compounds ((+/-)-5c, (+/-)-5d, and (+/-)-5v) were used for in vivo studies in mice, showing a decrease in MAGL activity and increased 2-arachidonoyl-sn-glycerol levels in forebrain tissue. In particular, 5v is characterized by a high eudysmic ratio and (3R,4S)-5v is one of the most potent irreversible inhibitors of h/mMAGL identified thus far. These results suggest that the new MAGL inhibitors have therapeutic potential for different central and peripheral pathologies.

			Development of Potent and Selective Monoacylglycerol Lipase Inhibitors. SARs, Structural Analysis, and Biological Characterization.,Butini S, Grether U, Jung KM, Ligresti A, Allara M, Postmus AGJ, Maramai S, Brogi S, Papa A, Carullo G, Sykes D, Veprintsev D, Federico S, Grillo A, Di Guglielmo B, Ramunno A, Stevens AF, Heer D, Lamponi S, Gemma S, Benz J, Di Marzo V, van der Stelt M, Piomelli D, Campiani G J Med Chem. 2024 Feb 8;67(3):1758-1782. doi: 10.1021/acs.jmedchem.3c01278. Epub , 2024 Jan 19. PMID:38241614<ref>PMID:38241614</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8ptr" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:59, 21 February 2024

2024-02-21T10:59:44Z

← Older revision		Revision as of 10:59, 21 February 2024
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	== 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 ==~~
	New potent, selective monoacylglycerol lipase (MAGL) inhibitors based on the azetidin-2-one scaffold ((+/-)-5a-v, (+/-)-6a-j, and (+/-)-7a-d) were developed as irreversible ligands, as demonstrated by enzymatic and crystallographic studies for (+/-)-5d, (+/-)-5l, and (+/-)-5r. X-ray analyses combined with extensive computational studies allowed us to clarify the binding mode of the compounds. 5v was identified as selective for MAGL when compared with other serine hydrolases. Solubility, in vitro metabolic stability, cytotoxicity, and absence of mutagenicity were determined for selected analogues. The most promising compounds ((+/-)-5c, (+/-)-5d, and (+/-)-5v) were used for in vivo studies in mice, showing a decrease in MAGL activity and increased 2-arachidonoyl-sn-glycerol levels in forebrain tissue. In particular, 5v is characterized by a high eudysmic ratio and (3R,4S)-5v is one of the most potent irreversible inhibitors of h/mMAGL identified thus far. These results suggest that the new MAGL inhibitors have therapeutic potential for different central and peripheral pathologies.

	Development of Potent and Selective Monoacylglycerol Lipase Inhibitors. SARs, Structural Analysis, and Biological Characterization.,Butini S, Grether U, Jung KM, Ligresti A, Allara M, Postmus AGJ, Maramai S, Brogi S, Papa A, Carullo G, Sykes D, Veprintsev D, Federico S, Grillo A, Di Guglielmo B, Ramunno A, Stevens AF, Heer D, Lamponi S, Gemma S, Benz J, Di Marzo V, van der Stelt M, Piomelli D, Campiani G J Med Chem. 2024 Jan 19. doi: 10.1021/acs.jmedchem.3c01278. PMID:38241614<ref>PMID:38241614</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 8ptr" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:44, 1 February 2024

2024-02-01T11:44:49Z

← Older revision		Revision as of 11:44, 1 February 2024
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 8ptr is ~~ON HOLD until Paper~~ Publication		==COMPLEX CRYSTAL STRUCTURE OF MUTANT HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 5r==
			<StructureSection load='8ptr' size='340' side='right'caption='[[8ptr]], [[Resolution\|resolution]] 1.73Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[8ptr]] 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=8PTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PTR FirstGlance]. <br>
			</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.73Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFH:(3~{R},4~{S})-4-(1,3-benzodioxol-5-yl)-1-[1-(benzotriazol-1-ylcarbonyl)piperidin-4-yl]-3-(3-fluorophenyl)azetidin-2-one'>EFH</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=8ptr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ptr OCA], [https://pdbe.org/8ptr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ptr RCSB], [https://www.ebi.ac.uk/pdbsum/8ptr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ptr ProSAT]</span></td></tr>
			</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 ==
			New potent, selective monoacylglycerol lipase (MAGL) inhibitors based on the azetidin-2-one scaffold ((+/-)-5a-v, (+/-)-6a-j, and (+/-)-7a-d) were developed as irreversible ligands, as demonstrated by enzymatic and crystallographic studies for (+/-)-5d, (+/-)-5l, and (+/-)-5r. X-ray analyses combined with extensive computational studies allowed us to clarify the binding mode of the compounds. 5v was identified as selective for MAGL when compared with other serine hydrolases. Solubility, in vitro metabolic stability, cytotoxicity, and absence of mutagenicity were determined for selected analogues. The most promising compounds ((+/-)-5c, (+/-)-5d, and (+/-)-5v) were used for in vivo studies in mice, showing a decrease in MAGL activity and increased 2-arachidonoyl-sn-glycerol levels in forebrain tissue. In particular, 5v is characterized by a high eudysmic ratio and (3R,4S)-5v is one of the most potent irreversible inhibitors of h/mMAGL identified thus far. These results suggest that the new MAGL inhibitors have therapeutic potential for different central and peripheral pathologies.

	~~Authors: Butini, S~~., ~~Benz~~, J., Grether, U., ~~Leibrock~~, L., ~~Papa~~, A., Maramai, S., Carullo, G., Federico, S., Grillo, A., Di Guglielmo, B., Lamponi, S., ~~Gemma~~, S., Campiani, G.		Development of Potent and Selective Monoacylglycerol Lipase Inhibitors. SARs, Structural Analysis, and Biological Characterization.,Butini S, Grether U, Jung KM, Ligresti A, Allara M, Postmus AGJ, Maramai S, Brogi S, Papa A, Carullo G, Sykes D, Veprintsev D, Federico S, Grillo A, Di Guglielmo B, Ramunno A, Stevens AF, Heer D, Lamponi S, Gemma S, Benz J, Di Marzo V, van der Stelt M, Piomelli D, Campiani G J Med Chem. 2024 Jan 19. doi: 10.1021/acs.jmedchem.3c01278. PMID:38241614<ref>PMID:38241614</ref>

	~~Description~~: ~~COMPLEX CRYSTAL STRUCTURE OF MUTANT HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 5r~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased Structures~~]]		</div>
	[[Category: ~~Campiani, G~~]]		<div class="pdbe-citations 8ptr" style="background-color:#fffaf0;"></div>
	[[Category: ~~Di Guglielmo, B~~]]		== References ==
	[[Category: ~~Lamponi,~~ S]]		<references/>
	[[Category: ~~Federico, S~~]]		__TOC__
	[[Category: ~~Grether, U~~]]		</StructureSection>
	[[Category: ~~Papa, A~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Benz, J~~]]		[[Category: Large Structures]]
	[[Category: ~~Butini,~~ S]]		[[Category: Benz J]]
	[[Category: ~~Maramai, S~~]]		[[Category: Butini S]]
	[[Category: Grillo, A]]		[[Category: Campiani G]]
	[[Category: ~~Gemma,~~ S]]		[[Category: Carullo G]]
	[[Category: Leibrock, L]]		[[Category: Di Guglielmo B]]
	[[Category: ~~Carullo, G~~]]		[[Category: Federico S]]
			[[Category: Gemma S]]
			[[Category: Grether U]]
			[[Category: Grillo A]]
			[[Category: Lamponi S]]
			[[Category: Leibrock L]]
			[[Category: Maramai S]]
			[[Category: Papa A]]

OCA at 04:41, 23 August 2023

2023-08-23T04:41:46Z

← Older revision		Revision as of 04:41, 23 August 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8ptr is ON HOLD		The entry 8ptr is ON HOLD until Paper Publication

	Authors: Butini, S., Benz, J., Grether, U., Leibrock, L., Papa, A., Maramai, S., Carullo, G., Federico, S., Grillo, A., Di Guglielmo, B., Lamponi, S., Gemma, S., Campiani, G.		Authors: Butini, S., Benz, J., Grether, U., Leibrock, L., Papa, A., Maramai, S., Carullo, G., Federico, S., Grillo, A., Di Guglielmo, B., Lamponi, S., Gemma, S., Campiani, G.
Line 7:		Line 7:
	Description: COMPLEX CRYSTAL STRUCTURE OF MUTANT HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 5r		Description: COMPLEX CRYSTAL STRUCTURE OF MUTANT HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 5r
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	~~[[Category: Maramai, S]]~~
	[[Category: Campiani, G]]		[[Category: Campiani, G]]
	~~[[Category: Grillo, A]]~~
	[[Category: Di Guglielmo, B]]		[[Category: Di Guglielmo, B]]
	[[Category: Lamponi, S]]		[[Category: Lamponi, S]]
	[[Category: Federico, S]]		[[Category: Federico, S]]
	[[Category: Grether, U]]		[[Category: Grether, U]]
	~~[[Category: Gemma, S]]~~
	[[Category: Papa, A]]		[[Category: Papa, A]]
	[[Category: Benz, J]]		[[Category: Benz, J]]
			[[Category: Butini, S]]
			[[Category: Maramai, S]]
			[[Category: Grillo, A]]
			[[Category: Gemma, S]]
	[[Category: Leibrock, L]]		[[Category: Leibrock, L]]
	~~[[Category: Butini, S]]~~
	[[Category: Carullo, G]]		[[Category: Carullo, G]]

OCA: Protected "8ptr" [edit=sysop:move=sysop]

2023-07-26T10:57:46Z

Protected "8ptr" [edit=sysop:move=sysop]

← Older revision	Revision as of 10:57, 26 July 2023
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8ptr is ON HOLD Authors: Butini, S., Benz, J., Grether, U., Leibrock, L., Papa, A., Maramai, S., Carullo, G., Federico, S., Grillo, A., Di Guglielmo...

2023-07-26T10:57:42Z

New page: '''Unreleased structure''' The entry 8ptr is ON HOLD Authors: Butini, S., Benz, J., Grether, U., Leibrock, L., Papa, A., Maramai, S., Carullo, G., Federico, S., Grillo, A., Di Guglielmo...

New page

'''Unreleased structure'''

The entry 8ptr is ON HOLD

Authors: Butini, S., Benz, J., Grether, U., Leibrock, L., Papa, A., Maramai, S., Carullo, G., Federico, S., Grillo, A., Di Guglielmo, B., Lamponi, S., Gemma, S., Campiani, G.

Description: COMPLEX CRYSTAL STRUCTURE OF MUTANT HUMAN MONOGLYCERIDE LIPASE WITH COMPOUND 5r
[[Category: Unreleased Structures]]
[[Category: Maramai, S]]
[[Category: Campiani, G]]
[[Category: Grillo, A]]
[[Category: Di Guglielmo, B]]
[[Category: Lamponi, S]]
[[Category: Federico, S]]
[[Category: Grether, U]]
[[Category: Gemma, S]]
[[Category: Papa, A]]
[[Category: Benz, J]]
[[Category: Leibrock, L]]
[[Category: Butini, S]]
[[Category: Carullo, G]]