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Literature summary for 3.1.1.23 extracted from

  • King, A.R.; Lodola, A.; Carmi, C.; Fu, J.; Mor, M.; Piomelli, D.
    A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone-based enzyme inhibitors (2009), Br. J. Pharmacol., 157, 974-983.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.1.23

Cloned(Commentary)

Cloned (Comment) Organism
full-length cDNA subcloned into the pEF15b vector containing an N-terminal histidine tag and transformed in Escherichia coli DH5alpha. Positive clones expressed in Escherichia coli Rosetta 2(De3)pLysS cells. Expression of wild-type and mutants in HeLa cells Rattus norvegicus

Protein Variants

Protein Variants Comment Organism
C201G causes significant decreases in enzyme activity, albeit smaller than that produced by mutant C242G. Inhibitory potency of N-arachidonylmaleimide is selectively decreased Rattus norvegicus
C208G causes significant decreases in enzyme activity, albeit smaller than that produced by mutant C242G. Inhibitory potency of octhilinone is selectively decreased. Has no effect on the inhibitory potency of N-arachidonylmaleimide Rattus norvegicus
C242G produces a striking reduction in MGL activity, due to a decrease in maximal reaction velocity rather than a change in Michaelis constant. Inhibitory potency of N-arachidonylmaleimide is selectively decreased Rattus norvegicus
C301G has no effect on MGL activity Rattus norvegicus
C32G has no effect on MGL activity Rattus norvegicus
C55G has no effect on MGL activity Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
(5E)-5-(3-methylbutylidene)-2-thioxo-1,3-thiazolidin-4-one weak inhibitory effect Rattus norvegicus
2-methyl-4-isothiazolin-3-one
-
 Rattus norvegicus
2-octyl-4-isothiazolin-3-one octhilinone, inhibits purified recombinant MGL through a partially reversible mechanism that involves a specific interaction with cysteine 208 Rattus norvegicus
2-octyl-benzo[d]isothiazol-3-one
-
 Rattus norvegicus
2-oleoyl-4-isothiazolin-3-one
-
 Rattus norvegicus
3-methoxy-N-phenyl-1,2,4-thiadiazol-5-amine weak inhibitory effect Rattus norvegicus
additional information 3-methoxy-N-phenyl-1,2,4-thiadiazol-5-amine and 3-propoxy-2-benzofuran-1(3H)-one do not inhibit Rattus norvegicus
N-arachidonylmaleimide inhibitory effect is attributed to the ability of this compound to react with C242 and form a Michael addition product Rattus norvegicus
N-ethylmaleimide
-
 Rattus norvegicus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.098
-
 2-oleoylglycerol mutant C242G Rattus norvegicus
0.115
-
 2-oleoylglycerol wild-type Rattus norvegicus

Organism

Organism UniProt Comment Textmining
Rattus norvegicus
-
-
-

Purification (Commentary)

Purification (Comment) Organism
by gel filtration Rattus norvegicus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2-oleoylglycerol + H2O Cys208 plays an important role in MGL function Rattus norvegicus oleic acid + glycerol
-
 ?

Synonyms

Synonyms Comment Organism
MGL
-
 Rattus norvegicus
monoacylglycerol lipase
-
 Rattus norvegicus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00003
-
 wild-type, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus N-arachidonylmaleimide
0.000043
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus 2-oleoyl-4-isothiazolin-3-one
0.000046
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/mlL bovine serum albumin, fatty acid-free Rattus norvegicus N-arachidonylmaleimide
0.000059
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus 2-octyl-benzo[d]isothiazol-3-one
0.000107
-
 mutant C242G, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus N-arachidonylmaleimide
0.000151
-
 wild-type, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus 2-octyl-4-isothiazolin-3-one
0.000239
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus 2-methyl-4-isothiazolin-3-one
0.000442
-
 mutant C201G, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus N-arachidonylmaleimide
0.000722
-
 mutant C208G, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus 2-octyl-4-isothiazolin-3-one
0.0027
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus N-ethylmaleimide
0.02
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus (5E)-5-(3-methylbutylidene)-2-thioxo-1,3-thiazolidin-4-one
0.028
-
 recombinant purified enzyme, for 10 min at 37°C, in 50 mM Tris-HCl, pH 8.0, 0.5 mg/ml bovine serum albumin, fatty acid-free Rattus norvegicus 3-methoxy-N-phenyl-1,2,4-thiadiazol-5-amine