BRENDA - Enzyme Database

Burkholderia pseudomallei isocitrate lyase is a persistence factor in pulmonary melioidosis: implications for the development of isocitrate lyase inhibitors as novel antimicrobials

van Schaik, E.J.; Tom, M.; Woods, D.E.; Infect. Immun. 77, 4275-4283 (2009)

Data extracted from this reference:

Activating Compound
EC Number
Activating Compound
Commentary
Organism
Structure
4.1.3.1
acetate
activity of the ICL promoter is significantly upregulated during growth on acetate
Burkholderia pseudomallei
Application
EC Number
Application
Commentary
Organism
4.1.3.1
drug development
isocitrate lyase inhibitors can be developed for chronic infections but only for use in combination with effective antibiotics
Burkholderia pseudomallei
Cloned(Commentary)
EC Number
Commentary
Organism
4.1.3.1
pGSV3-lux ICL mutant
Burkholderia pseudomallei
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
4.1.3.1
Itaconic acid
potent competitive inhibitor of ICL, 1 mg/ml reduces the activity to 42% of the uninhibited control. Inhibition of ICL enzymatic activity during chronic infection of rats forces the infection into an acute phase
Burkholderia pseudomallei
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
4.1.3.1
Burkholderia pseudomallei
-
strains 1026b and DD503
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.1.3.1
isocitrate
-
704000
Burkholderia pseudomallei
succinate + glyoxylate
-
-
-
?
Activating Compound (protein specific)
EC Number
Activating Compound
Commentary
Organism
Structure
4.1.3.1
acetate
activity of the ICL promoter is significantly upregulated during growth on acetate
Burkholderia pseudomallei
Application (protein specific)
EC Number
Application
Commentary
Organism
4.1.3.1
drug development
isocitrate lyase inhibitors can be developed for chronic infections but only for use in combination with effective antibiotics
Burkholderia pseudomallei
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
4.1.3.1
pGSV3-lux ICL mutant
Burkholderia pseudomallei
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
4.1.3.1
Itaconic acid
potent competitive inhibitor of ICL, 1 mg/ml reduces the activity to 42% of the uninhibited control. Inhibition of ICL enzymatic activity during chronic infection of rats forces the infection into an acute phase
Burkholderia pseudomallei
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
4.1.3.1
isocitrate
-
704000
Burkholderia pseudomallei
succinate + glyoxylate
-
-
-
?
General Information
EC Number
General Information
Commentary
Organism
4.1.3.1
malfunction
inhibiting the activity of this enzyme during experimental chronic lung infection of rats forces the infection into an acute state, which can then be treated with antibiotics. If antibiotics are not provided in combination with isocitrate lyase inhibitors, the resulting infection overwhelms the host, resulting in death. ICL mutant is hypervirulent, it does not establish a chronic infection but establishes an acute infection. ICL mutants are significantly more cytotoxic than other strains. Complementation of the mutant strain restores the wild-type phenotype
Burkholderia pseudomallei
4.1.3.1
physiological function
isocitrate lyase is a persistence factor. ICL is not required for survival within unactivated murine macrophage cells
Burkholderia pseudomallei
General Information (protein specific)
EC Number
General Information
Commentary
Organism
4.1.3.1
malfunction
inhibiting the activity of this enzyme during experimental chronic lung infection of rats forces the infection into an acute state, which can then be treated with antibiotics. If antibiotics are not provided in combination with isocitrate lyase inhibitors, the resulting infection overwhelms the host, resulting in death. ICL mutant is hypervirulent, it does not establish a chronic infection but establishes an acute infection. ICL mutants are significantly more cytotoxic than other strains. Complementation of the mutant strain restores the wild-type phenotype
Burkholderia pseudomallei
4.1.3.1
physiological function
isocitrate lyase is a persistence factor. ICL is not required for survival within unactivated murine macrophage cells
Burkholderia pseudomallei