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Literature summary extracted from

  • Aschauer, P.; Zimmermann, R.; Breinbauer, R.; Pavkov-Keller, T.; Oberer, M.
    The crystal structure of monoacylglycerol lipase from M. tuberculosis reveals the basis for specific inhibition (2018), Sci. Rep., 8, 8948 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.1.1.23 drug development Differences in the binding pocket of mtbMGL compared to human MGL open the possibility for specific inhibition of MGL from the pathogen Mycobacterium tuberculosis and use in the human pathogen treatment Mycobacterium tuberculosis

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.1.1.23 gene Rv0183, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) CodonPlus Mycobacterium tuberculosis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.1.1.23 enzyme mtbMGL in open conformation, sitting drop vapor diffusion method and microseeding, mixing 500 nl of 10 mg/ml protein solution with 500 nl of crystallization solution containing 0.1 M carboxylic acids, 0.1 M sodium HEPES/MOPS, pH 7.5, 20% ethylene glycol, and 10% PEG 8000, 4 months, 20°C, microseeding by mixing of 400 nl protein solution with 400 nl crystallization solution and 200 nl seeding stock, containing 0.03 M NaNO3, 0.03 M Na2HPO4, 0.03 M (NH4)2SO4, 0.1 M Na HEPES/MOPS, pH 7.8, 12% MPD, 12% PEG 1000 and 12% PEG 3350, 2 weeks, 20°C, X-ray diffraction structure determination and analysis at 1.80 A resolution, molecular replacement using the PDB IDs 3PE6 and 1W53 as search templates Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.1.1.23 additional information Mycobacterium tuberculosis MGL cannot be inhibited with JZL-184, a known inhibitor of human MGL. Differences in the binding pocket of mtbMGL compared to human MGL impair JZL-184 inhibition, overview. The human enzyme has an amphipathic cap helix 1 whereas cap helix1 of mtbMGL is mostly hydrophobic. Structure-based analysis for potential inhibitors for mtbMGL. JZL-184 docking study, overview Mycobacterium tuberculosis

Organism

EC Number Organism UniProt Comment Textmining
3.1.1.23 Mycobacterium tuberculosis O07427
-
-
3.1.1.23 Mycobacterium tuberculosis ATCC 25618 O07427
-
-
3.1.1.23 Mycobacterium tuberculosis H37Rv O07427
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.1.1.23 recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) CodonPlus by nickel affinity chromatography and gel filtration Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.1.1.23 1-oleoyl-glycerol + H2O
-
 Mycobacterium tuberculosis oleate + glycerol
-
 ?
3.1.1.23 1-oleoyl-glycerol + H2O
-
 Mycobacterium tuberculosis H37Rv oleate + glycerol
-
 ?
3.1.1.23 1-oleoyl-glycerol + H2O
-
 Mycobacterium tuberculosis ATCC 25618 oleate + glycerol
-
 ?
3.1.1.23 additional information docking studies with the substrate 1-oleoyl-glycerol in the form of the tetrahedral reaction intermediate. In the best-docking mode, the polar glycerol moiety of the substrate is in direct interaction with catalytically important residues Ser110, His256, Glu257, Met111 and Leu39 from the core region and Tyr181 situated within helix 3 of the cap. No positional preference for sn-1(3) or 2-MGs has been reported for any MGL Mycobacterium tuberculosis ?
-
 ?
3.1.1.23 additional information docking studies with the substrate 1-oleoyl-glycerol in the form of the tetrahedral reaction intermediate. In the best-docking mode, the polar glycerol moiety of the substrate is in direct interaction with catalytically important residues Ser110, His256, Glu257, Met111 and Leu39 from the core region and Tyr181 situated within helix 3 of the cap. No positional preference for sn-1(3) or 2-MGs has been reported for any MGL Mycobacterium tuberculosis H37Rv ?
-
 ?
3.1.1.23 additional information docking studies with the substrate 1-oleoyl-glycerol in the form of the tetrahedral reaction intermediate. In the best-docking mode, the polar glycerol moiety of the substrate is in direct interaction with catalytically important residues Ser110, His256, Glu257, Met111 and Leu39 from the core region and Tyr181 situated within helix 3 of the cap. No positional preference for sn-1(3) or 2-MGs has been reported for any MGL Mycobacterium tuberculosis ATCC 25618 ?
-
 ?

Subunits

EC Number Subunits Comment Organism
3.1.1.23 More docking studies revealing numerous interactions of mtbMGL to recognize polar and apolar segments of the monoacylglycerol target substrate, and structure comparison with the human enzyme, overview. The three-dimensional structure of mtbMGL reveals an alpha/beta hydrolase fold with an open cap conformation Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
3.1.1.23 LH57_01015
-
 Mycobacterium tuberculosis
3.1.1.23 MGL Rv0183
-
 Mycobacterium tuberculosis
3.1.1.23 monoacylglycerol lipase
-
 Mycobacterium tuberculosis
3.1.1.23 mtbMGL
-
 Mycobacterium tuberculosis
3.1.1.23 Rv0183
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.1.1.23 37
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.1.1.23 8
-
 assay at Mycobacterium tuberculosis

General Information

EC Number General Information Comment Organism
3.1.1.23 additional information docking studies and structure comparison with the human enzyme, overview. The structure reveals remarkable similarities with MGL from humans (hMGL) in both, the cap region and the alpha/beta core Mycobacterium tuberculosis