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Literature summary extracted from

  • Lu, J.P.; Chai, S.C.; Ye, Q.Z.
    Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase (2010), J. Med. Chem., 53, 1329-1337.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.11.18 gene mapB or Rv2861c, recombinant expression of isozyme MetAP1c in enzyme-deficient Escherichia coli cells. Plasmid-expressed MtMetAP1c complements the essential function of MetAP in Escherichia coli and supports the cell growth Mycobacterium tuberculosis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.4.11.18 purified recombinant isozyme MetAP1c in complex with inhibitors 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole and 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine, hanging drop vapor diffusion method at room temperature, mxing of 10 mg/ml protein with 2 mM metal in 50 mM Tris, pH 8.0, and 150 mM NaCl, and inhibitor in a molar ratio of 5:1 or 10:1 of inhibitor to enzyme, with an equal volume of reservoir solution containing 100 mM Bis-Tris, pH 5.5, 1.4 M NH4SO4, and 15% glycerol for 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole, and 100 mM Bis-Tris, pH 5.5, 1.3 M NH4SO4, and 15% glycerol for 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine, X-ray diffraction structure determination and analysis at 1.4-1.88 A resolution, molecular replacement Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.11.18 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole
-
 Mycobacterium tuberculosis
3.4.11.18 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
-
 Mycobacterium tuberculosis
3.4.11.18 5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
-
 Mycobacterium tuberculosis
3.4.11.18 5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
-
 Mycobacterium tuberculosis
3.4.11.18 additional information identification of inhibitors with high selectivity toward the Fe(II)-form, the Mn(II)-form, or the Co(II) and Ni(II) forms of the enzyme, respectively, overview. Binding structure of inhibitors in the active site of isozyme MetAP1c, overview Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
3.4.11.18 additional information
-
 additional information metal binding kinetics, overview Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.4.11.18 Co2+ activates Mycobacterium tuberculosis
3.4.11.18 Fe2+ activates Mycobacterium tuberculosis
3.4.11.18 Mn2+ activates Mycobacterium tuberculosis
3.4.11.18 additional information MetAP is one of the dinuclear metallohydrolases. MetAP1c requires divalent cations for activity. Co2+ and Fe2+ show the tightest binding, while Ni2+ is the most efficient cofactor for the catalysis. Metal binding kinetics, overview Mycobacterium tuberculosis
3.4.11.18 Ni2+ activates Mycobacterium tuberculosis

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.4.11.18 31000
-
 about, recombinant detagged enzyme, gel filtration Mycobacterium tuberculosis

Organism

EC Number Organism UniProt Comment Textmining
3.4.11.18 Mycobacterium tuberculosis P9WK19 isozyme MetAP1c encoded by gene mapB
-
3.4.11.18 Mycobacterium tuberculosis H37Rv P9WK19 isozyme MetAP1c encoded by gene mapB
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.4.11.18 recombinant isozyme MetAP1c to homogeneity as apoenzyme Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.11.18 L-methionyl 4-methylcoumarin-7-amide + H2O fluorogenic substrate Mycobacterium tuberculosis L-methionine + 7-amino-4-methylcoumarin
-
 ?
3.4.11.18 L-methionyl 4-methylcoumarin-7-amide + H2O fluorogenic substrate Mycobacterium tuberculosis H37Rv L-methionine + 7-amino-4-methylcoumarin
-
 ?

Subunits

EC Number Subunits Comment Organism
3.4.11.18 monomer 1 * 31000, about, recombinant detagged enzyme, sequence calculation and gel filtration Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
3.4.11.18 MetAP
-
 Mycobacterium tuberculosis
3.4.11.18 methionine aminopeptidase
-
 Mycobacterium tuberculosis
3.4.11.18 More MetAP is one of the dinuclear metallohydrolases Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.4.11.18 37
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.4.11.18 7.5
-
 assay at Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.4.11.18 0.00024
-
 pH 7.5, 37°C, with Ni2+ Mycobacterium tuberculosis 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
3.4.11.18 0.00026
-
 pH 7.5, 37°C, with Co2+ Mycobacterium tuberculosis 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
3.4.11.18 0.00058
-
 pH 7.5, 37°C, with Ni2+ Mycobacterium tuberculosis 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole
3.4.11.18 0.0013
-
 pH 7.5, 37°C, with Ni2+ Mycobacterium tuberculosis 5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
3.4.11.18 0.002
-
 pH 7.5, 37°C, with Co2+ Mycobacterium tuberculosis 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole
3.4.11.18 0.002
-
 pH 7.5, 37°C, with Mn2+ Mycobacterium tuberculosis 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
3.4.11.18 0.0025
-
 pH 7.5, 37°C, with Ni2+ Mycobacterium tuberculosis 5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine