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Literature summary extracted from

  • Labar, G.; Bauvois, C.; Borel, F.; Ferrer, J.L.; Wouters, J.; Lambert, D.M.
    Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling (2010), ChemBioChem, 11, 218-227.
    View publication on PubMed

Application

EC Number Application Comment Organism
3.1.1.23 drug development structure of MAGL paves the way for future medicinal chemistry works aimed at the design of new drugs exploiting 2-arachidonoylglycerol transmission. MAGL is a hot therapeutic target, because the design of selective and potent inhibitors can provide unique tools to interfere with 2-arachidonoylglycerol degradation and to finely modulate the endocannabinoid signal Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.1.1.23 wild-type and mutants expressed in the Escherichia coli Rosetta strain Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.1.1.23 by the hanging drop method and under oil crystallization, native enzyme or selenomethionyl derivative, at 2.2 A resolution. Belongs to I222 space group, with two molecules per asymmetric unit. Docking of 2-arachidonoylglycerol highlights a hydrophobic and a hydrophilic cavity that accommodate the lipid into the catalytic site Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
3.1.1.23 C201A substantial decrease in the inhibitory potential Homo sapiens
3.1.1.23 C201A/C208A/C242A no significant inhibition by N-arachidonylmaleimide Homo sapiens
3.1.1.23 C208A increase in the inhibiting power of N-arachidonylmaleimide Homo sapiens
3.1.1.23 C208A/C242A increase in the inhibiting power of N-arachidonylmaleimide Homo sapiens
3.1.1.23 C242A very slight decrease in N-arachidonylmaleimide inhibitory potency Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.1.1.23 JZL184 is more potent than LY2183240. The p-nitrophenyl group fits better in the MAGL cavity than the corresponding substituent of LY2183240 Homo sapiens
3.1.1.23 LY2183240 is less potent than JZL184 Homo sapiens
3.1.1.23 N-arachidonylmaleimide Cys201 is the crucial residue in MAGL inhibition by N-arachidonylmaleimide Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
3.1.1.23 Homo sapiens Q99685
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.1.23 by a combination of streptactin and ion metal affinity chromatography Homo sapiens

Storage Stability

EC Number Storage Stability Organism
3.1.1.23 -80°C, 50 mM Tris buffer, 200 mM NaCl, 0.1% lauryl dimethylamine N-oxide, pH 9.5 Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.1.23 2-arachidonoylglycerol + H2O 2-arachidonoylglycerol is bound in the tetrahedral intermediate state to Ser122 Homo sapiens arachidonic acid + glycerol
-
 ?
3.1.1.23 2-oleoylglycerol + H2O
-
 Homo sapiens oleic acid + glycerol
-
 ?

Subunits

EC Number Subunits Comment Organism
3.1.1.23 dimer mass spectrometry Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
3.1.1.23 MAGL
-
 Homo sapiens
3.1.1.23 monoacylglycerol lipase
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.1.1.23 5.38
-
 mutant C201A, at 37°C for 10 min, pH 8.0, in 50 mM Tris buffer Homo sapiens N-arachidonylmaleimide
3.1.1.23 6.11
-
 mutant C242A, at 37°C for 10 min, pH 8.0, in 50 mM Tris buffer Homo sapiens N-arachidonylmaleimide
3.1.1.23 6.27
-
 wild-type, at 37°C for 10 min, pH 8.0, in 50 mM Tris buffer Homo sapiens N-arachidonylmaleimide
3.1.1.23 6.48
-
 mutant C208A/C242A, at 37°C for 10 min, pH 8.0, in 50 mM Tris buffer Homo sapiens N-arachidonylmaleimide
3.1.1.23 6.64
-
 mutant C208A, at 37°C for 10 min, pH 8.0, in 50 mM Tris buffer Homo sapiens N-arachidonylmaleimide

General Information

EC Number General Information Comment Organism
3.1.1.23 physiological function key actor in endocannabinoid signaling Homo sapiens