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Literature summary extracted from

  • Vickery, C.R.; Kosa, N.M.; Casavant, E.P.; Duan, S.; Noel, J.P.; Burkart, M.D.
    Structure, biochemistry, and inhibition of essential 4'-phosphopantetheinyl transferases from two species of Mycobacteria (2014), ACS Chem. Biol., 9, 1939-1944.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.8.7 recombinant expression of enzyme PptT as maltose-binding-protein fusion protein Mycobacterium tuberculosis
2.7.8.7 recombinant expression of enzyme PptT as maltose-binding-protein fusion protein Mycobacterium ulcerans

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.8.7 purified recombinant MBP-fusion enzyme, X-ray diffraction structure determination and analysis at 1.59 A resolution Mycobacterium tuberculosis
2.7.8.7 purified recombinant MBP-fusion enzyme, X-ray diffraction structure determination and analysis at 1.65 A resolution Mycobacterium ulcerans

Protein Variants

EC Number Protein Variants Comment Organism
2.7.8.7 D114N site-directed mutagenesis, the mutation eliminates the negative charge of one of the putative Mg2+ ligands, also abolishes phosphopantetheinylation activity of PptT, inactive mutant Mycobacterium tuberculosis
2.7.8.7 E109D site-directed mutagenesis, inactive mutant, no measurable catalytic activity Mycobacterium tuberculosis
2.7.8.7 E116Q site-directed mutagenesis, the mutant shows 500fold reduced activity compared to the wild-type enzyme Mycobacterium tuberculosis
2.7.8.7 E157Q site-directed mutagenesis, removal of the negative charge associated with the putative Mg2+ ligand/general base abolishes phosphopantetheinylation activity, inactive mutant Mycobacterium tuberculosis
2.7.8.7 R48A site-directed mutagenesis, the mutation disrupts 3'-phosphate binding, the activity is reduced by 20fold compared to the wild-type enzyme Mycobacterium tuberculosis
2.7.8.7 R56A site-directed mutagenesis, the mutation disrupts 3'-phosphate binding, the activity is reduced by 100fold compared to the wild-type enzyme Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.8.7 2'-deoxy-adenosine-3',5'-bisphosphate
-
Mycobacterium tuberculosis
2.7.8.7 6-nitroso-benzopyrone
-
Mycobacterium tuberculosis
2.7.8.7 adenosine-3',5'-bisphosphate
-
Mycobacterium tuberculosis
2.7.8.7 Bay 11-7085
-
Mycobacterium tuberculosis
2.7.8.7 Calmidazolium
-
Mycobacterium tuberculosis
2.7.8.7 CoA
-
Mycobacterium tuberculosis
2.7.8.7 guanidinyl-naltrindole
-
Mycobacterium tuberculosis
2.7.8.7 additional information no or poor inhibition by Bay 11-7085, benserazide, (-)-ephedrine hemisulfate, and mitoxantrone Mycobacterium tuberculosis
2.7.8.7 PD 404182
-
Mycobacterium tuberculosis
2.7.8.7 sanguinarine
-
Mycobacterium tuberculosis
2.7.8.7 SCH-202676
-
Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.8.7 Mg2+ required Mycobacterium tuberculosis
2.7.8.7 Mg2+ required Mycobacterium ulcerans

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.8.7 CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein] Mycobacterium tuberculosis
-
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
?
2.7.8.7 CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein] Mycobacterium ulcerans
-
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
?
2.7.8.7 CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein] Mycobacterium tuberculosis H37Rv
-
adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.7.8.7 Mycobacterium tuberculosis P9WQD3
-
-
2.7.8.7 Mycobacterium tuberculosis H37Rv P9WQD3
-
-
2.7.8.7 Mycobacterium ulcerans A0PU93 strain Agy99
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.8.7 recombinant MBP-fusion enzyme Mycobacterium tuberculosis
2.7.8.7 recombinant MBP-fusion enzyme Mycobacterium ulcerans

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.8.7 CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
-
Mycobacterium tuberculosis adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
?
2.7.8.7 CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
-
Mycobacterium ulcerans adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
?
2.7.8.7 CoA-[4'-phosphopantetheine] + apo-[acyl-carrier protein]
-
Mycobacterium tuberculosis H37Rv adenosine 3',5'-bisphosphate + holo-[acyl-carrier protein]
-
?

Subunits

EC Number Subunits Comment Organism
2.7.8.7 More enzyme MuPPT possesses a pseudodimeric fold characteristic of Sfp-type PPTases, three-dimensional structure comparisons, modeling, overview Mycobacterium ulcerans
2.7.8.7 More enzyme PptT possesses a pseudodimeric fold characteristic of Sfp-type PPTases, three-dimensional structure comparisons, modeling, overview Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
2.7.8.7 4'-phosphopantetheinyl transferase
-
Mycobacterium tuberculosis
2.7.8.7 4'-phosphopantetheinyl transferase
-
Mycobacterium ulcerans
2.7.8.7 MuPPT
-
Mycobacterium ulcerans
2.7.8.7 PPTase
-
Mycobacterium tuberculosis
2.7.8.7 PPTase
-
Mycobacterium ulcerans
2.7.8.7 PptT
-
Mycobacterium tuberculosis
2.7.8.7 Sfp-type PPTase
-
Mycobacterium tuberculosis
2.7.8.7 Sfp-type PPTase
-
Mycobacterium ulcerans

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.7.8.7 0.0005
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis SCH-202676
2.7.8.7 0.00078
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis adenosine-3',5'-bisphosphate
2.7.8.7 0.0008
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis SCH-202676
2.7.8.7 0.0011
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis CoA
2.7.8.7 0.0016
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis adenosine-3',5'-bisphosphate
2.7.8.7 0.002
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis Calmidazolium
2.7.8.7 0.0047
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis CoA
2.7.8.7 0.0049
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis Calmidazolium
2.7.8.7 0.0049
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis sanguinarine
2.7.8.7 0.0071
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis PD 404182
2.7.8.7 0.0074
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis 2'-deoxy-adenosine-3',5'-bisphosphate
2.7.8.7 0.0085
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis 2'-deoxy-adenosine-3',5'-bisphosphate
2.7.8.7 0.012
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis guanidinyl-naltrindole
2.7.8.7 0.017
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis 6-nitroso-benzopyrone
2.7.8.7 0.019
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis PD 404182
2.7.8.7 0.019
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis guanidinyl-naltrindole
2.7.8.7 0.022
-
with substrate VibB, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis sanguinarine
2.7.8.7 0.024
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis 6-nitroso-benzopyrone
2.7.8.7 0.03
-
with substrate MAS, recombinant enzyme, pH and temperature not specified in the publication Mycobacterium tuberculosis Bay 11-7085

General Information

EC Number General Information Comment Organism
2.7.8.7 additional information analysis and comparisons of cofactor binding and active site composition, CoA binding pocket, catalytic mechanism of PptT, overview. While important for CoA binding, Arg48 and Arg56 likely play very small roles in catalysis Mycobacterium tuberculosis
2.7.8.7 additional information analysis and comparisons of cofactor binding and active site composition, CoA binding pocket, overview Mycobacterium ulcerans
2.7.8.7 physiological function 4'-phosphopantetheinyl transferase post-translationally modifies carrier proteins with a phosphopantetheine moiety, an essential reaction. In Mycobacteria, the Sfp-type PPTase activates pathways necessary for the biosynthesis of cell wall components and small molecule virulence factors Mycobacterium tuberculosis
2.7.8.7 physiological function 4'-phosphopantetheinyl transferase post-translationally modifies carrier proteins with a phosphopantetheine moiety, an essential reaction. In Mycobacteria, the Sfp-type PPTase activates pathways necessary for the biosynthesis of cell wall components and small molecule virulence factors Mycobacterium ulcerans