| IED ID | IndEnz0005000001 |
| Enzyme Type ID | lipase000001 |
| Protein Name |
Triacylglycerol lipase EC 3.1.1.3 Esterase/lipase Triolein hydrolase Cleaved into: Cytosolic triacylglycerol lipase; Extracellular triacylglycerol lipase |
| Gene Name | lipY PE-PGRS63 Rv3097c LH57_16905 |
| Organism | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Actinobacteria Actinomycetia (high G+C Gram-positive bacteria) Corynebacteriales Mycobacteriaceae Mycobacterium Mycobacterium tuberculosis complex Mycobacterium tuberculosis Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Enzyme Sequence | MVSYVVALPEVMSAAATDVASIGSVVATASQGVAGATTTVLAAAEDEVSAAIAALFSGHGQDYQALSAQLAVFHERFVQALTGAAKGYAAAELANASLLQSEFASGIGNGFATIHQEIQRAPTALAAGFTQVPPFAAAQAGIFTGTPSGAAGFDIASLWPVKPLLSLSALETHFAIPNNPLLALIASDIPPLSWFLGNSPPPLLNSLLGQTVQYTTYDGMSVVQITPAHPTGEYVVAIHGGAFILPPSIFHWLNYSVTAYQTGATVQVPIYPLVQEGGTAGTVVPAMAGLISTQIAQHGVSNVSVVGDSAGGNLALAAAQYMVSQGNPVPSSMVLLSPWLDVGTWQISQAWAGNLAVNDPLVSPLYGSLNGLPPTYVYSGSLDPLAQQAVVLEHTAVVQGAPFSFVLAPWQIHDWILLTPWGLLSWPQINQQLGIAA |
| Enzyme Length | 437 |
| Uniprot Accession Number | I6Y2J4 |
| Absorption | |
| Active Site | ACT_SITE 309; /evidence=ECO:0000305|PubMed:16354661; ACT_SITE 383; /evidence=ECO:0000250|UniProtKB:O06350; ACT_SITE 413; /evidence=ECO:0000250|UniProtKB:O06350 |
| Activity Regulation | ACTIVITY REGULATION: [Cytosolic triacylglycerol lipase]: PE domain down-regulates lipase activity. {ECO:0000269|PubMed:17938218, ECO:0000269|PubMed:26270534, ECO:0000269|PubMed:29986895, ECO:0000269|PubMed:31034693}.; ACTIVITY REGULATION: [Extracellular triacylglycerol lipase]: Cleavage by PecA does not affect surface localization and lipase activity. {ECO:0000269|PubMed:31662454}.; ACTIVITY REGULATION: Inhibited by diethyl-p-nitrophenyl phosphate (E-600) at 0.5 uM, by phenylmethanesulfonyl fluoride at 5 mM and by polyethylene glycol sorbitan monolaurate (Tween 20). Also inhibited by CaCl(2), CoCl(2), MnCl(2), ZnCl(2) and MgCl(2) (PubMed:16354661). Inhibited by several hydrazides compounds (PubMed:23684389). Stimulated slightly by SDS at concentrations up to 2 mM, above which the activity is severely inhibited (PubMed:16354661). {ECO:0000269|PubMed:16354661, ECO:0000269|PubMed:23684389}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; Evidence={ECO:0000269|PubMed:16354661}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + di-(9Z)-octadecenoylglycerol + H(+); Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945; Evidence={ECO:0000269|PubMed:16354661, ECO:0000269|PubMed:31034693}; CATALYTIC ACTIVITY: Reaction=an acetyl ester + H2O = acetate + an aliphatic alcohol + H(+); Xref=Rhea:RHEA:12957, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:47622; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=a butanoate ester + H2O = an aliphatic alcohol + butanoate + H(+); Xref=Rhea:RHEA:47348, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:50477; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=a hexanoate ester + H2O = an aliphatic alcohol + H(+) + hexanoate; Xref=Rhea:RHEA:47352, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17120, ChEBI:CHEBI:87656; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=an octanoate ester + H2O = an aliphatic alcohol + H(+) + octanoate; Xref=Rhea:RHEA:47356, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:87657; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=a dodecanoate ester + H2O = an aliphatic alcohol + dodecanoate + H(+); Xref=Rhea:RHEA:47364, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:87659; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=a tetradecanoate ester + H2O = an aliphatic alcohol + H(+) + tetradecanoate; Xref=Rhea:RHEA:47388, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30807, ChEBI:CHEBI:87691; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=H2O + hexadecanoate ester = an aliphatic alcohol + H(+) + hexadecanoate; Xref=Rhea:RHEA:47392, ChEBI:CHEBI:2571, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25835; Evidence={ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=H2O + octadecanoate ester = an aliphatic alcohol + H(+) + octadecanoate; Xref=Rhea:RHEA:47396, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25629, ChEBI:CHEBI:75925; Evidence={ECO:0000269|PubMed:23684389, ECO:0000269|PubMed:26398213}; CATALYTIC ACTIVITY: Reaction=1-butyrylglycerol + H2O = butanoate + glycerol + H(+); Xref=Rhea:RHEA:44324, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:17968, ChEBI:CHEBI:76503; Evidence={ECO:0000269|PubMed:29986895}; CATALYTIC ACTIVITY: Reaction=1,2,3-tributanoylglycerol + H2O = butanoate + dibutanoylglycerol + H(+); Xref=Rhea:RHEA:40475, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:35020, ChEBI:CHEBI:76478; Evidence={ECO:0000269|PubMed:29986895, ECO:0000269|PubMed:31034693}; |
| DNA Binding | |
| EC Number | 3.1.1.3 |
| Enzyme Function | FUNCTION: Catalyzes the hydrolysis of both intracellular and extracellular triacylglycerol (TAG) (PubMed:16354661, PubMed:17938218, PubMed:21471225, PubMed:29986895, PubMed:31034693). In vitro, can also hydrolyze p-nitrophenyl (pNP) esters with various chain lengths, including pNP-acetate (C2), pNP-butyrate (C4), pNP-caproate (C6), pNP-caprylate (C8), pNP-laurate (C12), pNP-myristate (C14), pNP-palmitate (C16) and pNP-stearate (C18) (PubMed:23684389, PubMed:26398213). Also hydrolyzes monobutyrin, tributyrin and trioctanoin (PubMed:29986895). Overexpression results in increase of virulence characterized by reduced survival of infected mouse and increased burden of bacilli in the lungs (PubMed:24631199). Hydrolyzes internal or host-derived TAG depending on its localization (PubMed:29986895). {ECO:0000269|PubMed:16354661, ECO:0000269|PubMed:17938218, ECO:0000269|PubMed:21471225, ECO:0000269|PubMed:23684389, ECO:0000269|PubMed:24631199, ECO:0000269|PubMed:26398213, ECO:0000269|PubMed:29986895, ECO:0000269|PubMed:31034693}.; FUNCTION: [Cytosolic triacylglycerol lipase]: Hydrolyzes TAG that accumulates within mycobacterial intracytosolic lipid inclusions (ILI) (PubMed:29986895). Probably responsible for the utilization of stored long-chain TAG during the dormancy and reactivation stages of the pathogen (PubMed:16354661). {ECO:0000269|PubMed:16354661, ECO:0000269|PubMed:29986895}.; FUNCTION: [Extracellular triacylglycerol lipase]: Hydrolyzes host-derived TAG. {ECO:0000269|PubMed:29986895}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is between 8 and 9. {ECO:0000269|PubMed:16354661}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (2); Domain (1); Motif (1); Region (2); Site (1) |
| Keywords | Cell wall;Cytoplasm;Hydrolase;Lipid degradation;Lipid metabolism;Reference proteome;Secreted;Virulence |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Cytosolic triacylglycerol lipase]: Cytoplasm {ECO:0000269|PubMed:29986895}.; SUBCELLULAR LOCATION: [Extracellular triacylglycerol lipase]: Secreted {ECO:0000269|PubMed:21471225, ECO:0000269|PubMed:29986895, ECO:0000269|PubMed:31034693, ECO:0000269|PubMed:31662454}. Secreted, cell wall {ECO:0000269|PubMed:17938218, ECO:0000269|PubMed:29986895, ECO:0000269|PubMed:31034693}. Cell surface {ECO:0000269|PubMed:17938218, ECO:0000269|PubMed:21471225, ECO:0000269|PubMed:29986895, ECO:0000269|PubMed:31034693, ECO:0000269|PubMed:31662454}. Note=Exported to the cell surface via the ESX-5 / type VII secretion system (T7SS). {ECO:0000269|PubMed:21471225, ECO:0000269|PubMed:31034693, ECO:0000269|PubMed:31662454}. |
| Modified Residue | |
| Post Translational Modification | PTM: Upon export, the PE domain is removed by proteolytic cleavage (PubMed:21471225, PubMed:31662454). Cleavage occurs at the cell surface and is not required for secretion (PubMed:31662454). Cleaved after Gly-149 by the aspartic protease PecA. May also be cleaved before Leu-98 and after Ala-136 (PubMed:31662454). {ECO:0000269|PubMed:21471225, ECO:0000269|PubMed:31662454}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 239..241; /note=Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole; /evidence=ECO:0000250|UniProtKB:Q5NUF3 |
| Gene Encoded By | |
| Mass | 45,023 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=7.57 mM for triolein (glyceryl trioleate) {ECO:0000269|PubMed:16354661}; Vmax=653.3 nmol/min/mg enzyme with triolein (glyceryl trioleate) as substrate {ECO:0000269|PubMed:16354661}; |
| Metal Binding | |
| Rhea ID | RHEA:12044; RHEA:38575; RHEA:12957; RHEA:47348; RHEA:47352; RHEA:47356; RHEA:47364; RHEA:47388; RHEA:47392; RHEA:47396; RHEA:44324; RHEA:40475 |
| Cross Reference Brenda |