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Literature summary for 3.1.1.23 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
Search for more literature for 3.1.1.23

Application

Application Comment Organism
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)

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

Crystallization (Commentary)

Crystallization (Comment) Organism
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

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

Inhibitors

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

Organism

Organism UniProt Comment Textmining
Homo sapiens Q99685
-
-

Purification (Commentary)

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

Storage Stability

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

Substrates and Products (Substrate)

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

Subunits

Subunits Comment Organism
dimer mass spectrometry Homo sapiens

Synonyms

Synonyms Comment Organism
MAGL
-
 Homo sapiens
monoacylglycerol lipase
-
 Homo sapiens

IC50 Value

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

General Information

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