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Literature summary extracted from

  • Dunn, M.F.; Ramirez-Trujillo, J.A.; Hernandez-Lucas, I.
    Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis (2009), Microbiology, 155, 3166-3175.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
4.1.3.1 additional information high enzymic activity of ICL in strains isolated from diabetic patients suffering from vulvovaginal candidiasis. Specific activation of ICL1 when the pathogen is exposed to neutrophils or macrophages Candida albicans
4.1.3.1 additional information ICL activity increases in pellicles in synthetic media as a consequence of fatty acid degradation as well as under microaerophilic growth conditions Mycobacterium tuberculosis

Application

EC Number Application Comment Organism
4.1.3.1 additional information constitutive enzymic activity can be used to identify Yersinia pestis in humans, animals, water, soil and food Yersinia pestis

Protein Variants

EC Number Protein Variants Comment Organism
2.3.3.9 D631N no activity Escherichia coli
2.3.3.9 R338K 6% of wild-type activity Escherichia coli

Inhibitors

EC Number Inhibitors Comment Organism Structure
4.1.3.1 additional information natural glyoxylate cycle inhibitors such 5-hydroxyindole-type alkaloids are potent inhibitors Candida albicans
4.1.3.1 additional information extracts of Illicium verum and Zingiber officinale inhibit ICL Mycobacterium tuberculosis
4.1.3.1 additional information halisulfates from the tropical sponge Hippospongia sp. are able to inhibit ICL activity, appressorium formation and C2 utilization Pyricularia grisea

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
4.1.3.1 peroxisome
-
Colletotrichum lagenaria 5777
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.3.9 Mg2+
-
Escherichia coli

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.3.3.9 65000
-
x * 65000 Escherichia coli
2.3.3.9 80000
-
1 * 80000 Escherichia coli
4.1.3.1 50000
-
-
Mycobacterium tuberculosis

Organism

EC Number Organism UniProt Comment Textmining
2.3.3.9 Bradyrhizobium japonicum
-
-
-
2.3.3.9 Candida albicans
-
-
-
2.3.3.9 Escherichia coli
-
-
-
2.3.3.9 Mycobacterium tuberculosis
-
-
-
2.3.3.9 Paracoccidioides brasiliensis
-
-
-
2.3.3.9 Parastagonospora nodorum
-
-
-
2.3.3.9 Rhizobium leguminosarum
-
-
-
2.3.3.9 Rhodococcus fascians
-
-
-
2.3.3.9 Sinorhizobium meliloti
-
-
-
2.3.3.9 Xanthomonas campestris
-
-
-
2.3.3.9 Yersinia enterocolitica
-
-
-
2.3.3.9 Yersinia pestis
-
-
-
2.3.3.9 Yersinia pseudotuberculosis
-
-
-
4.1.3.1 Aspergillus fumigatus
-
-
-
4.1.3.1 Aspergillus nidulans
-
-
-
4.1.3.1 Brucella suis
-
-
-
4.1.3.1 Candida albicans
-
-
-
4.1.3.1 Colletotrichum lagenaria
-
-
-
4.1.3.1 Cryptococcus neoformans
-
-
-
4.1.3.1 Escherichia coli
-
-
-
4.1.3.1 Leptosphaeria maculans
-
-
-
4.1.3.1 Mycobacterium avium
-
-
-
4.1.3.1 Mycobacterium tuberculosis
-
-
-
4.1.3.1 Paracoccidioides brasiliensis
-
-
-
4.1.3.1 Pseudomonas aeruginosa
-
-
-
4.1.3.1 Pyricularia grisea
-
-
-
4.1.3.1 Rhizobium tropici
-
-
-
4.1.3.1 Rhodococcus equi
-
-
-
4.1.3.1 Salmonella enterica subsp. enterica serovar Typhimurium
-
-
-
4.1.3.1 Sinorhizobium meliloti
-
-
-
4.1.3.1 Talaromyces marneffei
-
-
-
4.1.3.1 Yersinia enterocolitica
-
-
-
4.1.3.1 Yersinia pestis
-
-
-
4.1.3.1 Yersinia pseudotuberculosis
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
4.1.3.1 appressorium
-
Pyricularia grisea
-
4.1.3.1 appressorium
-
Colletotrichum lagenaria
-
4.1.3.1 conidium
-
Pyricularia grisea
-
4.1.3.1 conidium
-
Colletotrichum lagenaria
-
4.1.3.1 conidium
-
Aspergillus fumigatus
-
4.1.3.1 hypha
-
Pyricularia grisea
-
4.1.3.1 hypha
-
Colletotrichum lagenaria
-
4.1.3.1 hypha
-
Aspergillus fumigatus
-
4.1.3.1 mycelium
-
Pyricularia grisea
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.1.3.1 isocitrate
-
Pseudomonas aeruginosa succinate + glyoxylate
-
?
4.1.3.1 additional information Lys-193, Cys-195, His-197 and His-356 are catalytic, active-site residues, while His-184 is involved in the assembly of the tetrameric enzyme Escherichia coli ?
-
?

Subunits

EC Number Subunits Comment Organism
2.3.3.9 monomer 1 * 80000 Escherichia coli
2.3.3.9 multimer x * 65000 Escherichia coli
4.1.3.1 tetramer
-
Escherichia coli

Synonyms

EC Number Synonyms Comment Organism
2.3.3.9 malate synthase
-
Sinorhizobium meliloti
2.3.3.9 malate synthase
-
Bradyrhizobium japonicum
2.3.3.9 malate synthase
-
Mycobacterium tuberculosis
2.3.3.9 malate synthase
-
Candida albicans
2.3.3.9 malate synthase
-
Yersinia pseudotuberculosis
2.3.3.9 malate synthase
-
Yersinia pestis
2.3.3.9 malate synthase
-
Xanthomonas campestris
2.3.3.9 malate synthase
-
Rhizobium leguminosarum
2.3.3.9 malate synthase
-
Yersinia enterocolitica
2.3.3.9 malate synthase
-
Paracoccidioides brasiliensis
2.3.3.9 malate synthase
-
Rhodococcus fascians
2.3.3.9 malate synthase
-
Parastagonospora nodorum
2.3.3.9 malate synthase A
-
Escherichia coli
2.3.3.9 malate synthase G
-
Escherichia coli
4.1.3.1 AceA
-
Pseudomonas aeruginosa
4.1.3.1 AceA
-
Mycobacterium avium
4.1.3.1 AceA
-
Mycobacterium tuberculosis
4.1.3.1 AceA
-
Yersinia pestis
4.1.3.1 acuD
-
Aspergillus fumigatus
4.1.3.1 acuD
-
Paracoccidioides brasiliensis
4.1.3.1 ICL
-
Salmonella enterica subsp. enterica serovar Typhimurium
4.1.3.1 ICL
-
Sinorhizobium meliloti
4.1.3.1 ICL
-
Escherichia coli
4.1.3.1 ICL
-
Aspergillus nidulans
4.1.3.1 ICL
-
Pseudomonas aeruginosa
4.1.3.1 ICL
-
Mycobacterium avium
4.1.3.1 ICL
-
Yersinia pseudotuberculosis
4.1.3.1 ICL
-
Yersinia pestis
4.1.3.1 ICL
-
Rhodococcus equi
4.1.3.1 ICL
-
Aspergillus fumigatus
4.1.3.1 ICL
-
Yersinia enterocolitica
4.1.3.1 ICL
-
Rhizobium tropici
4.1.3.1 ICL
-
Paracoccidioides brasiliensis
4.1.3.1 ICL
-
Brucella suis
4.1.3.1 ICL
-
Talaromyces marneffei
4.1.3.1 ICL1
-
Mycobacterium tuberculosis
4.1.3.1 ICL1
-
Candida albicans
4.1.3.1 ICL1
-
Cryptococcus neoformans
4.1.3.1 ICL1
-
Pyricularia grisea
4.1.3.1 ICL1
-
Colletotrichum lagenaria
4.1.3.1 ICL1
-
Leptosphaeria maculans
4.1.3.1 ICL2
-
Mycobacterium tuberculosis
4.1.3.1 isocitrate lyase
-
Salmonella enterica subsp. enterica serovar Typhimurium
4.1.3.1 isocitrate lyase
-
Sinorhizobium meliloti
4.1.3.1 isocitrate lyase
-
Escherichia coli
4.1.3.1 isocitrate lyase
-
Aspergillus nidulans
4.1.3.1 isocitrate lyase
-
Pseudomonas aeruginosa
4.1.3.1 isocitrate lyase
-
Mycobacterium avium
4.1.3.1 isocitrate lyase
-
Mycobacterium tuberculosis
4.1.3.1 isocitrate lyase
-
Candida albicans
4.1.3.1 isocitrate lyase
-
Yersinia pseudotuberculosis
4.1.3.1 isocitrate lyase
-
Yersinia pestis
4.1.3.1 isocitrate lyase
-
Cryptococcus neoformans
4.1.3.1 isocitrate lyase
-
Rhodococcus equi
4.1.3.1 isocitrate lyase
-
Pyricularia grisea
4.1.3.1 isocitrate lyase
-
Colletotrichum lagenaria
4.1.3.1 isocitrate lyase
-
Aspergillus fumigatus
4.1.3.1 isocitrate lyase
-
Leptosphaeria maculans
4.1.3.1 isocitrate lyase
-
Yersinia enterocolitica
4.1.3.1 isocitrate lyase
-
Rhizobium tropici
4.1.3.1 isocitrate lyase
-
Paracoccidioides brasiliensis
4.1.3.1 isocitrate lyase
-
Brucella suis
4.1.3.1 isocitrate lyase
-
Talaromyces marneffei

Expression

EC Number Organism Comment Expression
2.3.3.9 Parastagonospora nodorum decrease in transcription after germination, increase of activity after germination down
2.3.3.9 Yersinia pseudotuberculosis during growth on acetate up
2.3.3.9 Yersinia enterocolitica during growth on acetate up
2.3.3.9 Xanthomonas campestris during infection of tomato plants up
2.3.3.9 Candida albicans in the presence of macrophages up
2.3.3.9 Paracoccidioides brasiliensis in the presence of macrophages up
4.1.3.1 Candida albicans in bloodstream infection, ICL is downregulated in the initial stages of infection (10 min) down
4.1.3.1 Pyricularia grisea during infection, significant ICL gene expression in conidia, appressoria, mycelia and hyphae up
4.1.3.1 Talaromyces marneffei expressed in macrophages up
4.1.3.1 Cryptococcus neoformans ICL in a rabbit meningitis model is upregulated after 7 days in the subarachnoid space up
4.1.3.1 Mycobacterium tuberculosis increased aceA (icl) mRNA expression in response to human macrophages. ICL mRNA levels markedly increase in lungs of mice and in human lung granulomas, as well as in the lymphocyte region of necrotic granulomas up
4.1.3.1 Yersinia pseudotuberculosis induced during growth on acetate but not on xylose up
4.1.3.1 Yersinia enterocolitica induced during growth on acetate but not on xylose up
4.1.3.1 Candida albicans is induced in Candida albicans exposed to human neutrophils. In bloodstream infection, ICL is upregulated beginning about 20 min after infection and reaches a 20fold increase after 60 min. ICL expression is detected during growth on Casamino acids, glutamate or peptone, and under starvation conditions up
4.1.3.1 Paracoccidioides brasiliensis transcript level of the ICL gene increases following phagocytosis by murine macrophages. After macrophage internalization of conidia the ICL-encoding gene (acuD) is highly expressed up

General Information

EC Number General Information Comment Organism
4.1.3.1 malfunction a mutant deleted of the ICL gene (acuD) is fully virulent in a murine model Aspergillus fumigatus
4.1.3.1 malfunction an ICL-deficient mutant is unable to utilize acetate, ethanol, citrate, glycerol, oleate, lactate, pyruvate, peptone, glutamate or alanine for growth, unlike the parental strain. ICL-deficient mutant is unable to utilize nonfermentable carbon sources and has reduced virulence in mice Candida albicans
4.1.3.1 malfunction an ICL1 mutant shows the same number of subarachnoidal yeast cells as the wild-type after 10 days in immunosuppressed rabbits. In an inhalation model of murine cryptococcosis, no differences in survival between an ICL1 mutant and the wild-type Cryptococcus neoformans
4.1.3.1 malfunction deletion of the ICL1 gene causes a reduction in appressorium formation, conidiogenesis and cuticle penetration, and an overall decrease in damage to leaves of rice and barley Pyricularia grisea
4.1.3.1 malfunction ICL (aceA) mutant displays reduced virulence on alfalfa seedlings and a reduction in histopathology in rat lungs Pseudomonas aeruginosa
4.1.3.1 malfunction ICL1 mutant fails to grow on acetate or fatty acids, but is able to germinate and develop appressoria and is capable of degrading lipid bodies as well as the wild-type strain. Conidia from the ICL1-deficient mutant inoculated onto cucumber leaves and cotyledons form a reduced number of lesions on leaves, and especially on cotyledons, but nevertheless remain pathogenic. In invasive experiments such as the inoculation of conidia into wound sites, no defect is observed in the ICL1 mutant, while in penetration assays on cucumber cotyledons the mutant is unable to develop penetrating hyphae Colletotrichum lagenaria
4.1.3.1 malfunction mutations in the sole ICL gene (aceA) prevent growth on acetate but do not affect pathogenesis in a mouse model Yersinia pestis
4.1.3.1 malfunction population of an ICL-deficient strain increases in macrophages after 12 h but then decline significantly Rhodococcus equi
4.1.3.1 malfunction single ICL mutations have no dramatic effect on the growth. ICL mutant has a reduced ability to sustain the infection. An ICL/AceA double mutant is unable to grow on carbon source. The double mutant inoculated into mice is eliminated from lungs and spleen and is unable to induce splenomegaly or alterations in lungs Mycobacterium tuberculosis
4.1.3.1 physiological function ICL is essential for full virulence in the organism Pyricularia grisea
4.1.3.1 physiological function ICL is essential for long-term survival and proliferation in macrophages Rhodococcus equi
4.1.3.1 physiological function ICL is required for persistence during chronic infection, but not for acute lethal infection in mice Salmonella enterica subsp. enterica serovar Typhimurium
4.1.3.1 physiological function ICL1 contributes to virulence but is not essential for systemic infection. Role for the beta-oxidation pathway in virulence Candida albicans
4.1.3.1 physiological function important role for ICL in fungal virulence on plants. The ICL1 gene is expressed during its infection of Brassica napus cotyledons and inactivation of this locus causes low germination rates of pycnidiospores, reducing the pathogenicity of the fungus on cotyledons as well as limiting its hyphal growth on canola Leptosphaeria maculans
4.1.3.1 physiological function lack of correlation between ICL gene expression and biological function Cryptococcus neoformans
4.1.3.1 physiological function the glyoxylate cycle mediated by ICL is unnecessary for virulence Brucella suis
4.1.3.1 physiological function the organism constitutively produces ICL Yersinia pestis
4.1.3.1 physiological function two functional ICLs Mycobacterium avium
4.1.3.1 physiological function two functional ICLs. ICL has a pivotal role in bacterial persistence in the host. ICL activity is essential for survival in the host. ICL and to a lesser extent AceA are required for the growth on propionate and on odd-chain fatty acids as a carbon source. The organism possesses dual ICL/MICL activity and can support growth on acetate and propionate Mycobacterium tuberculosis