| IED ID | IndEnz0005000300 |
| Enzyme Type ID | lipase000300 |
| Protein Name |
Monoacylglycerol lipase MGL EC 3.1.1.23 |
| Gene Name | Rv0183 LH57_01015 |
| 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 | MTTTRTERNFAGIGDVRIVYDVWTPDTAPQAVVVLAHGLGEHARRYDHVAQRLGAAGLVTYALDHRGHGRSGGKRVLVRDISEYTADFDTLVGIATREYPGCKRIVLGHSMGGGIVFAYGVERPDNYDLMVLSAPAVAAQDLVSPVVAVAAKLLGVVVPGLPVQELDFTAISRDPEVVQAYNTDPLVHHGRVPAGIGRALLQVGETMPRRAPALTAPLLVLHGTDDRLIPIEGSRRLVECVGSADVQLKEYPGLYHEVFNEPERNQVLDDVVAWLTERL |
| Enzyme Length | 279 |
| Uniprot Accession Number | O07427 |
| Absorption | |
| Active Site | ACT_SITE 110; /note="Nucleophile"; /evidence="ECO:0000305|PubMed:17784850, ECO:0000305|PubMed:29895832"; ACT_SITE 226; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:17784850, ECO:0000305|PubMed:29895832"; ACT_SITE 256; /note="Charge relay system"; /evidence="ECO:0000305|PubMed:17784850, ECO:0000305|PubMed:29895832" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by the serine esterase inhibitors PMSF (100%), E600 (80%) and THL (22%) (PubMed:17784850). Virtual screening identified a tautomer of ZINC13451138, known inhibitor for HIV-1 integrase, as a potential inhibitor (Probable). {ECO:0000269|PubMed:17784850, ECO:0000305|PubMed:22405030}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a 1-acylglycerol + H2O = a fatty acid + glycerol + H(+); Xref=Rhea:RHEA:34019, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:28868, ChEBI:CHEBI:35759; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.; EC=3.1.1.23; Evidence={ECO:0000269|PubMed:17784850}; 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:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44325; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=1-octanoylglycerol + H2O = glycerol + H(+) + octanoate; Xref=Rhea:RHEA:44328, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:25646, ChEBI:CHEBI:85241; Evidence={ECO:0000269|PubMed:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44329; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=1-decanoylglycerol + H2O = decanoate + glycerol + H(+); Xref=Rhea:RHEA:44320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:27689, ChEBI:CHEBI:75547; Evidence={ECO:0000269|PubMed:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44321; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+); Xref=Rhea:RHEA:44316, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:18262, ChEBI:CHEBI:75539; Evidence={ECO:0000269|PubMed:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44317; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=1-tetradecanoylglycerol + H2O = glycerol + H(+) + tetradecanoate; Xref=Rhea:RHEA:44312, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30807, ChEBI:CHEBI:75562; Evidence={ECO:0000269|PubMed:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44313; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000269|PubMed:17784850}; CATALYTIC ACTIVITY: Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:73990; Evidence={ECO:0000269|PubMed:17784850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492; Evidence={ECO:0000269|PubMed:17784850}; |
| DNA Binding | |
| EC Number | 3.1.1.23 |
| Enzyme Function | FUNCTION: Involved in the hydrolysis of exogenous host lipids during chronic infection (Probable). Catalyzes the hydrolysis of both monoacylglycerols (MAG) and diacylglycerols (DAG), with a preference for MAG. It hydrolyzes 2-MAG, 1-3-MAG and MAG with short, medium and long chain fatty acids such as 1-monobutyroyl-rac-glycerol (MC4), 1-mono-octanoyl-rac-glycerol (MC8), 1-monodecanoyl-rac-glycerol (MC10), 1-monolauroyl-rac-glycerol (MC12), 1-monomyristoyl-rac-glycerol (MC14) and 1-mono-oleyl-rac-glycerol (MC18:1) (PubMed:17784850). Also able to hydrolyze DAG with short (DiC6) and medium (DiC10) fatty acid chains, but not with longest fatty acid chains (PubMed:17784850). Can also hydrolyze vinyl laurate (VC12), vinyl butyrate (VC4) and vinyl propionate (VC3) (PubMed:17784850). {ECO:0000269|PubMed:17784850, ECO:0000305|PubMed:17784850, ECO:0000305|PubMed:22405030}.; FUNCTION: Induces an inflammatory response and cell apoptosis in the host cells. Increases expression of IL-6, NF-kappaB, TLR-2, TLR-6, TNF-alpha, and MyD88 in mouse alveolar macrophage RAW264.7 cells. Persistent expression induces RAW264.7 cell apoptosis in vitro. {ECO:0000269|PubMed:21076482}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 55 degrees Celsius. The activity increases 3-fold in a linear fashion from 25 to 50 degrees Celsius before decreasing slowly at higher temperatures. {ECO:0000269|PubMed:17784850}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9. Highly stable from pH 7.5 to 9.0. At lower pH values, the residual activity decreases rapidly to 50% at pH 6.5, and it is completely abolished after 1 hour of incubation at pH levels of 6.0 and below. {ECO:0000269|PubMed:17784850}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (10); Chain (1); Helix (12); Mutagenesis (3); Turn (2) |
| Keywords | 3D-structure;Cell wall;Hydrolase;Lipid degradation;Lipid metabolism;Pharmaceutical;Reference proteome;Secreted;Virulence |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:17784850}. Secreted {ECO:0000305|PubMed:17784850}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (3) |
| Cross Reference PDB | 6EIC; 7OZM; 7P0Y; |
| Mapped Pubmed ID | 34572512; |
| Motif | |
| Gene Encoded By | |
| Mass | 30,262 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:34019; RHEA:44324; RHEA:44325; RHEA:44328; RHEA:44329; RHEA:44320; RHEA:44321; RHEA:44316; RHEA:44317; RHEA:44312; RHEA:44313; RHEA:38487; RHEA:38488; RHEA:38491; RHEA:38492 |
| Cross Reference Brenda | 3.1.1.23; |