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Literature summary for 3.4.11.18 extracted from

  • Lu, J.P.; Ye, Q.Z.
    Expression and characterization of Mycobacterium tuberculosis methionine aminopeptidase type 1a (2010), Bioorg. Med. Chem. Lett., 20, 2776-2779.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the MetAP isozymes are potential targets to develop antitubercular therapeutics Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
expression of the His-tagged isozyme MetAP1a as apoenzyme Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole
-
Mycobacterium tuberculosis
4-(2-methyl-1,3-thiazol-4-yl)benzene-1,2-diol
-
Mycobacterium tuberculosis
4-(3-methylthiophen-2-yl)benzene-1,2-diol
-
Mycobacterium tuberculosis
5-(2,5-dichlorophenyl)furan-2-carboxylic acid
-
Mycobacterium tuberculosis
5-(2-chlorophenyl)furan-2-carboxylic acid
-
Mycobacterium tuberculosis
5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
-
Mycobacterium tuberculosis
5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
-
Mycobacterium tuberculosis
5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
-
Mycobacterium tuberculosis
additional information a set of inhibitors displayed completely different inhibitory profiles on the two mycobacterial MetAPs in both potency and metalloform selectivity Mycobacterium tuberculosis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.011
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Ni2+ Mycobacterium tuberculosis
0.082
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Co2+ Mycobacterium tuberculosis
0.161
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Fe2+ Mycobacterium tuberculosis
0.17
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Mn2+ Mycobacterium tuberculosis

Metals/Ions

Metals/Ions Comment Organism Structure
Co2+ activates, tight binding to the enzyme Mycobacterium tuberculosis
Fe2+ activates, tight binding to the enzyme Mycobacterium tuberculosis
additional information poor activation by Mn2+ Mycobacterium tuberculosis
Ni2+ most efficient activator, tight binding to the enzyme Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis
-
two isozymes MtMetAP1a and MtMetAP1c
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged isozyme MetAP1a in apoenzyme form Mycobacterium tuberculosis

Source Tissue

Source Tissue Comment Organism Textmining
additional information the two MetAP isozymes, MtMetAP1a and MtMetAP1c, are expressed at different levels in growing and stationary phases Mycobacterium tuberculosis
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-methionine-4-methylcoumarin-7-amide + H2O fluorogenic substrate Mycobacterium tuberculosis L-methionine + 7-amino-4-methylcoumarin
-
?
additional information MetAP carries out the cotranslational N-terminal methionine excision Mycobacterium tuberculosis ?
-
?

Subunits

Subunits Comment Organism
More differing active site structures of isozymes MetAP1a and MetAP1c Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
MetAP
-
Mycobacterium tuberculosis
MetAP1a
-
Mycobacterium tuberculosis
methionine aminopeptidase
-
Mycobacterium tuberculosis
methionine aminopeptidase type 1a
-
Mycobacterium tuberculosis
More MetAP belongs to the family of dinuclear metallohydrolases Mycobacterium tuberculosis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.014
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Fe2+ Mycobacterium tuberculosis
0.045
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Ni2+ Mycobacterium tuberculosis
0.07
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Mn2+ Mycobacterium tuberculosis
0.36
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Co2+ Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000031 0.0007 recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 4-(2-methyl-1,3-thiazol-4-yl)benzene-1,2-diol
0.00007 0.0023 recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 4-(3-methylthiophen-2-yl)benzene-1,2-diol
0.02 0.25 recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 5-(2-chlorophenyl)furan-2-carboxylic acid
0.205 0.25 and above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 5-[(2,4-dichlorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
0.25
-
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 5-(2,5-dichlorophenyl)furan-2-carboxylic acid
0.25
-
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 5-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
0.25
-
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 5-[(4-methylbenzyl)sulfanyl]-4H-1,2,4-triazol-3-amine
0.25
-
above, recombinant isozyme MetAP1a in presence of different divalent metal ions, overview Mycobacterium tuberculosis 3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole

General Information

General Information Comment Organism
physiological function MetAP is essential for bacterial survival Mycobacterium tuberculosis

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.41
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Mn2+ Mycobacterium tuberculosis
0.87
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Fe2+ Mycobacterium tuberculosis
4.39
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Co2+ Mycobacterium tuberculosis
40.91
-
L-methionine-4-methylcoumarin-7-amide recombinant isozyme MetAP1a in presence of Ni2+ Mycobacterium tuberculosis