P9WKK6 · ACEA1_MYCTO
- ProteinIsocitrate lyase 1
- Geneicl1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids428 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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
- D-threo-isocitrate = glyoxylate + succinate
Cofactor
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 μM | threo-D-isocitrate | 6.8 | 37 | |||
188 μM | threo-DL-isocitrate (ICA) | 6.8 | ||||
718 μM | DL-threo-2-methylisocitrate (MICA) | 7.5 |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
1.3 μmol/min/mg | 6.8 | 37 | with 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 91-93 | substrate | ||||
Sequence: SGW | ||||||
Binding site | 153 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Active site | 191 | Proton acceptor | ||||
Sequence: C | ||||||
Binding site | 192-193 | substrate | ||||
Sequence: GH | ||||||
Binding site | 228 | substrate | ||||
Sequence: R | ||||||
Binding site | 313-317 | substrate | ||||
Sequence: NCSPS | ||||||
Binding site | 347 | substrate | ||||
Sequence: T |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | isocitrate lyase activity | |
Molecular Function | metal ion binding | |
Molecular Function | methylisocitrate lyase activity | |
Biological Process | glyoxylate cycle | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameIsocitrate lyase 1
- EC number
- Short namesICL1
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium > Mycobacterium tuberculosis complex
Accessions
- Primary accessionP9WKK6
- Secondary accessions
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000427637 | 1-428 | Isocitrate lyase 1 | |||
Sequence: MSVVGTPKSAEQIQQEWDTNPRWKDVTRTYSAEDVVALQGSVVEEHTLARRGAEVLWEQLHDLEWVNALGALTGNMAVQQVRAGLKAIYLSGWQVAGDANLSGHTYPDQSLYPANSVPQVVRRINNALQRADQIAKIEGDTSVENWLAPIVADGEAGFGGALNVYELQKALIAAGVAGSHWEDQLASEKKCGHLGGKVLIPTQQHIRTLTSARLAADVADVPTVVIARTDAEAATLITSDVDERDQPFITGERTREGFYRTKNGIEPCIARAKAYAPFADLIWMETGTPDLEAARQFSEAVKAEYPDQMLAYNCSPSFNWKKHLDDATIAKFQKELAAMGFKFQFITLAGFHALNYSMFDLAYGYAQNQMSAYVELQEREFAAEERGYTATKHQREVGAGYFDRIATTVDPNSSTTALTGSTEEGQFH |
Expression
Induction
Induced by palmitate and acetate. Repressed by glucose and succinate.
Interaction
Subunit
Homotetramer.
Structure
Sequence
- Sequence statusComplete
- Length428
- Mass (Da)47,087
- Last updated2014-04-16 v1
- ChecksumE5223F38CB5D9E8B
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE000516 EMBL· GenBank· DDBJ | AAK44707.1 EMBL· GenBank· DDBJ | Genomic DNA |