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Literature summary for 2.7.9.1 extracted from

  • Wu, C.; Dunaway-Mariano, D.; Mariano, P.
    Design, synthesis, and evaluation of inhibitors of pyruvate phosphate dikinase (2013), J. Org. Chem., 78, 1910-1922.
    View publication on PubMed
Search for more literature for 2.7.9.1

Application

Application Comment Organism
drug development based on its role in the metabolism of microbial human pathogens, PPDK is a potential drug target [Clostridium] symbiosum

Inhibitors

Inhibitors Comment Organism Structure
4'-aminobutyl-5,7-dihydroxyflavone displays selectivity for inhibition of PPDK versus other enzymes that utilize ATP and NAD+ [Clostridium] symbiosum
4'-aminohexyl-5,7-dihydroxyflavone a potent competitive PPDK inhibitor with an IC50 value of 0.0016 mM [Clostridium] symbiosum
4'-aminopropyl-5,7-dihydroxyflavone derivative specifically targets the ATP binding site and inhibits catalysis of only the PPDK + ATP + phosphate -> PPDK-P + AMP diphosphate partial reaction during single turnover experiments [Clostridium] symbiosum
additional information screening of substances that bind to the PPDK ATP-grasp domain active site reveals that flavone analogues are potent inhibitors of the Clostridium symbiosum PPDK. In silico modeling studies suggest that placement of a 3–6 carbon-tethered ammonium substituent at the 3'- or 4'-positions of 5,7-dihydroxyflavones result in favorable electrostatic interactions with the PPDK Mg-ATP binding site. Synthesis of polymethylene-tethered amine derivatives of 5,7-dihydroxyflavones [Clostridium] symbiosum

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required [Clostridium] symbiosum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + pyruvate + phosphate [Clostridium] symbiosum
-
 AMP + phosphoenolpyruvate + diphosphate
-
 r

Organism

Organism UniProt Comment Textmining
[Clostridium] symbiosum
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + pyruvate + phosphate
-
 [Clostridium] symbiosum AMP + phosphoenolpyruvate + diphosphate
-
 r
ATP + pyruvate + phosphate the enzyme forms phosphoenolpyruvate via two partial reactions: pyruvate phosphate dikinase + ATP + phosphate -> [pyruvate phosphate dikinase]-phosphate + AMP + diphosphate and [pyruvate phosphate dikinase]-phosphate + pyruvate -> phosphoenolpyruvate + pyruvate phosphate dikinase [Clostridium] symbiosum AMP + phosphoenolpyruvate + diphosphate
-
 r

Synonyms

Synonyms Comment Organism
PPDK
-
 [Clostridium] symbiosum
pyruvate phosphate dikinase
-
 [Clostridium] symbiosum

Cofactor

Cofactor Comment Organism Structure
AMP
-
 [Clostridium] symbiosum
ATP
-
 [Clostridium] symbiosum

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
 additional information inhibitor steady-state kinetic analysis [Clostridium] symbiosum
0.0016
-
 4'-aminohexyl-5,7-dihydroxyflavone pH and temperature not specified in the publication [Clostridium] symbiosum