General Information of the Molecule (ID: Mol00980)
Name
Isocitrate lyase 1 (ICL1) ,Mycobacterium tuberculosis
Synonyms
ICL1; Isocitrase; Isocitratase; Methylisocitrate lyase; MICA; MT0483
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Molecule Type
Protein
Gene Name
icl1
Gene ID
45424429
Sequence
MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQL
HDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQV
VRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSH
WEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSD
VDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEA
VKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFD
LAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTG
STEEGQFH
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Function
Involved in the persistence and virulence of M.tuberculosis. Catalyzes the reversible formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle, which operates as an anaplerotic route for replenishing the tricarboxylic acid cycle during growth on fatty acid substrates. It also catalyzes the formation of pyruvate and succinate from 2-methylisocitrate, a key step in the methylcitrate cycle (propionate degradation route).
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Uniprot ID
ACEA1_MYCTO
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Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: Corynebacteriales
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis
Type(s) of Resistant Mechanism of This Molecule
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
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Isoniazid
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: HIV-infected patients with tuberculosis [1]
Resistant Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Resistant Drug Isoniazid
Molecule Alteration Expression
Up-regulation
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Mycobacterium tuberculosis strains 1773
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MIC assay
Mechanism Description Despite targeting diverse cellular processes, all three drugs trigger activation of Mtb's isocitrate lyases (ICLs), metabolic enzymes commonly assumed to be involved in replenishing of tricarboxylic acid (TCA) cycle intermediates. We further show that ICL-deficient Mtb strains are significantly more susceptible than wild-type Mtb to all three antibiotics, and that this susceptibility can be chemically rescued when Mtb is co-incubated with an antioxidant.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: HIV-infected patients with tuberculosis [1]
Sensitive Disease HIV-infected patients with tuberculosis [ICD-11: 1C60.0]
Sensitive Drug Isoniazid
Molecule Alteration Expression
Down-regulation
Experimental Note Discovered Using In-vivo Testing Model
In Vitro Model Mycobacterium tuberculosis strains 1773
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MIC assay
Mechanism Description Despite targeting diverse cellular processes, all three drugs trigger activation of Mtb's isocitrate lyases (ICLs), metabolic enzymes commonly assumed to be involved in replenishing of tricarboxylic acid (TCA) cycle intermediates. We further show that ICL-deficient Mtb strains are significantly more susceptible than wild-type Mtb to all three antibiotics, and that this susceptibility can be chemically rescued when Mtb is co-incubated with an antioxidant.
References
Ref 1 Isocitrate lyase mediates broad antibiotic tolerance in Mycobacterium tuberculosis. Nat Commun. 2014 Jun 30;5:4306. doi: 10.1038/ncomms5306.

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