Literature summary for 3.4.11.18 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.

Search for more literature for 3.4.11.18

Cloned(Commentary)

Cloned (Comment)	Organism
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)

Crystallization (Comment)	Organism
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

Crystallization (Comment)

Organism

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

Inhibitors	Comment	Organism
3-[(4-fluorobenzyl)sulfanyl]-4H-1,2,4-triazole	-	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	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]

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

Metals/Ions

Metals/Ions	Comment	Organism
Co2+	activates	Mycobacterium tuberculosis
Fe2+	activates	Mycobacterium tuberculosis
Mn2+	activates	Mycobacterium tuberculosis
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
Ni2+	activates	Mycobacterium tuberculosis

Molecular Weight [Da]

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

Organism

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

Purification (Commentary)

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

Substrates and Products (Substrate)

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

Subunits

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

Synonyms

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

Temperature Optimum [°C]

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

pH Optimum

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

IC50 Value

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