P9WKK6 · ACEA1_MYCTO

Function

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).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Can also use Mn2+ ion.

Activity regulation

Inhibited by itaconate, itaconic anhydride, bromopyruvate and 3-nitropropionate (3-NP), when M.tuberculosis grows on fatty acids, but not on glucose. At 5 mM, oxalate and malate also inhibit the activity to approximately 50%.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
145 μMthreo-D-isocitrate6.837
188 μMthreo-DL-isocitrate (ICA)6.8
718 μMDL-threo-2-methylisocitrate (MICA)7.5
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
1.3 μmol/min/mg6.837with threo-D-isocitrate as substrate
kcat is 5.24 sec-1 for isocitrate lyase activity with threo-DL-isocitrate as substrate (at pH 6). kcat is 1.25 sec-1 for methylisocitrate lyase activity with DL-threo-2-methylisocitrate as substrate (at pH 7.5).

pH Dependence

Optimum pH is 6.8.

Pathway

Carbohydrate metabolism; glyoxylate cycle; (S)-malate from isocitrate: step 1/2.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site91-93substrate
Binding site153Mg2+ (UniProtKB | ChEBI)
Active site191Proton acceptor
Binding site192-193substrate
Binding site228substrate
Binding site313-317substrate
Binding site347substrate

GO annotations

AspectTerm
Molecular Functionisocitrate lyase activity
Molecular Functionmetal ion binding
Molecular Functionmethylisocitrate lyase activity
Biological Processglyoxylate cycle
Biological Processtricarboxylic acid cycle

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Isocitrate lyase 1
  • EC number
  • Short names
    ICL1
  • Alternative names
    • Isocitrase
    • Isocitratase
    • Methylisocitrate lyase
      (MICA
      ) (EC:4.1.3.30
      ) . EC:4.1.3.30 (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      icl1
    • Ordered locus names
      MT0483

Organism names

Accessions

  • Primary accession
    P9WKK6
  • Secondary accessions
    • L0T3N9
    • O53752
    • P0A5H3

Proteomes

Phenotypes & Variants

Disruption phenotype

Deletion of icl1 has little effect on replication in media containing glycerol, glucose, short-chain fatty acids or long-chain fatty acids. Deletion of icl1 results in a modest reduction of the bacterial load in the lungs during the chronic phase but not the acute phase of infection, and reduces tissue pathology. Deletion of both icl1 and icl2 eliminates growth on fatty acids but has little effect on use of carbohydrates. Cells lacking both genes are incapable of growth in mice and are rapidly eliminated from the lungs and spleen.

Chemistry

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004276371-428Isocitrate lyase 1

Expression

Induction

Induced by palmitate and acetate. Repressed by glucose and succinate.

Interaction

Subunit

Homotetramer.

Structure

Family & Domains

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    428
  • Mass (Da)
    47,087
  • Last updated
    2014-04-16 v1
  • Checksum
    E5223F38CB5D9E8B
MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQLHDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQVVRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSHWEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSDVDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEAVKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFDLAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTGSTEEGQFH

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AE000516
EMBL· GenBank· DDBJ
AAK44707.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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