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Literature summary for 3.1.1.116 extracted from

  • Hsu, K.L.; Tsuboi, K.; Adibekian, A.; Pugh, H.; Masuda, K.; Cravatt, B.F.
    DAGLbeta inhibition perturbs a lipid network involved in macrophage inflammatory responses (2012), Nat. Chem. Biol., 8, 999-1007 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.1.116

Protein Variants

Protein Variants Comment Organism
additional information generation of mutant Daglbeta-/- mice, analysis of the membrane proteome of transiently transfected HEK-293T cells overexpressing mouse DAGLbeta. Using a combination of inhibitors and knockout mice, strong evidence is generated that both DAGLbeta and PLA2G4A contribute to prostaglandin production in lipopolysaccharide-stimulated macrophages Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
(2-benzylpiperidin-1-yl)[4-(2'-methoxy[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone
-
 Mus musculus
(2-benzylpiperidin-1-yl)[4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone
-
 Mus musculus
(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacine-3-yl)-N-(2-phenylethyl)-N-(5-propanamidopentyl)-4-[4-(trifluoromethoxy)phenyl]-1H-1,2,3-triazole-1-carboxamide probe HT-01 labels both DAGLbeta and DAGLalpha. HT-01 is about 5fold more active against DAGLbeta than FP-Rh Mus musculus
fluorophosphonate-rhodamine FP-Rh, in this probe the fluorophosphonate is the reactive group (RG) as it binds irreversibly to the active-site serine nucleophile of serine hydrolases and the tag is rhodamine, a fluorophore for in-gel visualization Mus musculus
additional information a series of in vivo-active 1,2,3-triazole urea inhibitors, along with paired negative-control and activity-based probes, are used for the functional analysis of DAGLbeta in living systems. Optimized inhibitors show excellent selectivity for DAGLbeta over other serine hydrolases, including DAGLalpha (about 60fold selectivity), and the limited off-targets, such as ABHD6, are also inhibited by the negative-control probe. Establishment of a DAGL activity assay based on competitive ABPP methods using a fluorophosphonate-rhodamine (FP-Rh) probe, labeling is blocked by the non-specific lipase inhibitor tetrahydrolipstatin in a dose-dependent manner. Opening the piperidyl ring of DAGLbeta inhibitors facilitates attachment of a BODIPY fluorophore to yield probe HT-01, which labels both DAGLbeta and DAGLalpha. HT-01 is about 5fold more active against DAGLbeta than FP-Rh. In situ treatment of Neuro2A cells and peritoneal macrophages with inhibitors, overview Mus musculus
RHC80267 a non-selective serine hydrolase inhibitor Mus musculus
tetrahydrolipstatin a non-selective serine hydrolase inhibitor, non-specific lipase inhibitor Mus musculus
[4-(4'-methoxy[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl](2-phenylpiperidin-1-yl)methanone
-
 Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane
-
 Mus musculus 16020
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O Mus musculus
-
 2-arachidonoylglycerol + fatty acid
-
 r

Organism

Organism UniProt Comment Textmining
Mus musculus Q91WC9
-
-

Source Tissue

Source Tissue Comment Organism Textmining
macrophage peritoneal macrophages Mus musculus
-
Neuro-2a cell
-
 Mus musculus
-
neuroblastoma cell
-
 Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O
-
 Mus musculus 2-arachidonoylglycerol + fatty acid
-
 r
additional information establishment of a DAGL activity assay based on competitive ABPP methods using a fluorophosphonate-rhodamine (FP-Rh) probe, labeling is blocked by the non-specific lipase inhibitor tetrahydrolipstatin in a dose-dependent manner. Opening the piperidyl ring of DAGLbeta inhibitors facilitates attachment of a BODIPY fluorophore to yield probe HT-01, which labels both DAGLbeta and DAGLalpha. HT-01 is about 5fold more active against DAGLbeta than FP-Rh Mus musculus ?
-
-

Synonyms

Synonyms Comment Organism
DAGLbeta
-
 Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.2
-
 assay at Mus musculus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000071
-
 pH 7.2, 37°C Mus musculus (2-benzylpiperidin-1-yl)[4-(2'-methoxy[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone
0.000082
-
 pH 7.2, 37°C Mus musculus (2-benzylpiperidin-1-yl)[4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl]methanone
0.01
-
 above, pH 7.2, 37°C Mus musculus [4-(4'-methoxy[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl](2-phenylpiperidin-1-yl)methanone

General Information

General Information Comment Organism
malfunction DAGLbeta inhibition perturbs a lipid network involved in macrophage inflammatory responses. DAGLbeta inactivation lowers 2-arachidonoylglycerol (2-AG) content, as well as arachidonic acid and eicosanoids contents, in mouse peritoneal macrophages in a manner that is distinct and complementary to disruption of cytosolic phospholipase-A2 (PLA2G4A). A corresponding reduction in lipopolysaccharide-induced tumor necrosis factor-alpha release is observed Mus musculus
physiological function the endocannabinoid 2-arachidonoylglycerol (2-AG) is biosynthesized by diacylglycerol lipases DAGLalpha and DAGLbeta. DAGLbeta is a key metabolic hub within a lipid network that regulates proinflammatory responses in macrophages. Using a combination of inhibitors and knockout mice, strong evidence is generated that both DAGLbeta and PLA2G4A contribute to prostaglandin production in lipopolysaccharide-stimulated macrophages Mus musculus