MGLL_MYCTU
ID MGLL_MYCTU Reviewed; 279 AA.
AC O07427; F2GLY1; I6Y308; L0T2S2;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Monoacylglycerol lipase {ECO:0000303|PubMed:17784850};
DE Short=MGL {ECO:0000303|PubMed:17784850};
DE EC=3.1.1.23 {ECO:0000269|PubMed:17784850};
GN OrderedLocusNames=Rv0183; ORFNames=LH57_01015;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP SER-110; ASP-226 AND HIS-256, ACTIVITY REGULATION, ACTIVE SITE, MASS
RP SPECTROMETRY, SUBCELLULAR LOCATION, AND SUBSTRATE SPECIFICITY.
RC STRAIN=H37Rv;
RX PubMed=17784850; DOI=10.1042/bj20070745;
RA Cotes K., Dhouib R., Douchet I., Chahinian H., de Caro A., Carriere F.,
RA Canaan S.;
RT "Characterization of an exported monoglyceride lipase from Mycobacterium
RT tuberculosis possibly involved in the metabolism of host cell membrane
RT lipids.";
RL Biochem. J. 408:417-427(2007).
RN [4]
RP FUNCTION IN VIRULENCE.
RX PubMed=21076482; DOI=10.1139/w10-079;
RA Xu G., Jia H., Li Y., Liu X., Li M., Wang Y.;
RT "Hemolytic phospholipase Rv0183 of Mycobacterium tuberculosis induces
RT inflammatory response and apoptosis in alveolar macrophage RAW264.7
RT cells.";
RL Can. J. Microbiol. 56:916-924(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, AND IDENTIFICATION AS A DRUG TARGET.
RC STRAIN=H37Rv;
RX PubMed=22405030; DOI=10.1111/j.1747-0285.2012.01373.x;
RA Saravanan P., Dubey V.K., Patra S.;
RT "Potential selective inhibitors against Rv0183 of Mycobacterium
RT tuberculosis targeting host lipid metabolism.";
RL Chem. Biol. Drug Des. 79:1056-1062(2012).
RN [7]
RP POTENTIAL USE AS A BIOMARKER.
RX PubMed=29174965; DOI=10.1016/j.jinf.2017.11.004;
RA Liu Y., Li X., Liu W., Liu Y., Zhong Z., Wang L., Ge S., Zhang J., Xia N.;
RT "IL-6 release of Rv0183 antigen-stimulated whole blood is a potential
RT biomarker for active tuberculosis patients.";
RL J. Infect. 76:376-382(2018).
RN [8] {ECO:0007744|PDB:6EIC}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), SUBUNIT, AND ACTIVE SITE.
RX PubMed=29895832; DOI=10.1038/s41598-018-27051-7;
RA Aschauer P., Zimmermann R., Breinbauer R., Pavkov-Keller T., Oberer M.;
RT "The crystal structure of monoacylglycerol lipase from M. tuberculosis
RT reveals the basis for specific inhibition.";
RL Sci. Rep. 8:8948-8948(2018).
CC -!- FUNCTION: Involved in the hydrolysis of exogenous host lipids during
CC chronic infection (Probable). Catalyzes the hydrolysis of both
CC monoacylglycerols (MAG) and diacylglycerols (DAG), with a preference
CC for MAG. It hydrolyzes 2-MAG, 1-3-MAG and MAG with short, medium and
CC long chain fatty acids such as 1-monobutyroyl-rac-glycerol (MC4), 1-
CC mono-octanoyl-rac-glycerol (MC8), 1-monodecanoyl-rac-glycerol (MC10),
CC 1-monolauroyl-rac-glycerol (MC12), 1-monomyristoyl-rac-glycerol (MC14)
CC and 1-mono-oleyl-rac-glycerol (MC18:1) (PubMed:17784850). Also able to
CC hydrolyze DAG with short (DiC6) and medium (DiC10) fatty acid chains,
CC but not with longest fatty acid chains (PubMed:17784850). Can also
CC hydrolyze vinyl laurate (VC12), vinyl butyrate (VC4) and vinyl
CC propionate (VC3) (PubMed:17784850). {ECO:0000269|PubMed:17784850,
CC ECO:0000305|PubMed:17784850, ECO:0000305|PubMed:22405030}.
CC -!- FUNCTION: Induces an inflammatory response and cell apoptosis in the
CC host cells. Increases expression of IL-6, NF-kappaB, TLR-2, TLR-6, TNF-
CC alpha, and MyD88 in mouse alveolar macrophage RAW264.7 cells.
CC Persistent expression induces RAW264.7 cell apoptosis in vitro.
CC {ECO:0000269|PubMed:21076482}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acylglycerol + H2O = a fatty acid + glycerol + H(+);
CC Xref=Rhea:RHEA:34019, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:28868, ChEBI:CHEBI:35759;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-butyrylglycerol + H2O = butanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44324, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:17968, ChEBI:CHEBI:76503;
CC Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44325;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octanoylglycerol + H2O = glycerol + H(+) + octanoate;
CC Xref=Rhea:RHEA:44328, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:25646, ChEBI:CHEBI:85241;
CC Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44329;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-decanoylglycerol + H2O = decanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:27689, ChEBI:CHEBI:75547;
CC Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44321;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44316, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:18262, ChEBI:CHEBI:75539;
CC Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44317;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoylglycerol + H2O = glycerol + H(+) +
CC tetradecanoate; Xref=Rhea:RHEA:44312, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30807,
CC ChEBI:CHEBI:75562; Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44313;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:73990; Evidence={ECO:0000269|PubMed:17784850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- ACTIVITY REGULATION: Inhibited by the serine esterase inhibitors PMSF
CC (100%), E600 (80%) and THL (22%) (PubMed:17784850). Virtual screening
CC identified a tautomer of ZINC13451138, known inhibitor for HIV-1
CC integrase, as a potential inhibitor (Probable).
CC {ECO:0000269|PubMed:17784850, ECO:0000305|PubMed:22405030}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9. Highly stable from pH 7.5 to 9.0. At lower pH
CC values, the residual activity decreases rapidly to 50% at pH 6.5, and
CC it is completely abolished after 1 hour of incubation at pH levels of
CC 6.0 and below. {ECO:0000269|PubMed:17784850};
CC Temperature dependence:
CC Optimum temperature is 55 degrees Celsius. The activity increases 3-
CC fold in a linear fashion from 25 to 50 degrees Celsius before
CC decreasing slowly at higher temperatures.
CC {ECO:0000269|PubMed:17784850};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:29895832}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:17784850}. Secreted {ECO:0000305|PubMed:17784850}.
CC -!- MASS SPECTROMETRY: Mass=30223; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:17784850};
CC -!- PHARMACEUTICAL: The Rv0183 antigen-specific IL-6 response has the
CC potential to be used as an immune-diagnosis test for active TB in
CC clinical practice. {ECO:0000269|PubMed:29174965}.
CC -!- MISCELLANEOUS: Rv0183 represents a suitable and promising drug target.
CC {ECO:0000269|PubMed:22405030, ECO:0000269|PubMed:29895832}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. {ECO:0000305}.
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DR EMBL; CP009480; AIR12906.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP42909.1; -; Genomic_DNA.
DR RefSeq; NP_214697.2; NC_000962.3.
DR RefSeq; WP_003401112.1; NZ_NVQJ01000001.1.
DR PDB; 6EIC; X-ray; 1.80 A; A/B/C=1-279.
DR PDB; 7OZM; X-ray; 2.15 A; A=1-279.
DR PDB; 7P0Y; X-ray; 2.25 A; A/B=1-279.
DR PDBsum; 6EIC; -.
DR PDBsum; 7OZM; -.
DR PDBsum; 7P0Y; -.
DR AlphaFoldDB; O07427; -.
DR SMR; O07427; -.
DR STRING; 83332.Rv0183; -.
DR ChEMBL; CHEMBL2176861; -.
DR SwissLipids; SLP:000001038; -.
DR ESTHER; myctu-rv0183; Monoglyceridelipase_lysophospholip.
DR PaxDb; O07427; -.
DR PRIDE; O07427; -.
DR DNASU; 886785; -.
DR GeneID; 886785; -.
DR KEGG; mtu:Rv0183; -.
DR PATRIC; fig|83332.111.peg.210; -.
DR TubercuList; Rv0183; -.
DR eggNOG; COG2267; Bacteria.
DR HOGENOM; CLU_026209_7_2_11; -.
DR OMA; FHGFSDH; -.
DR PhylomeDB; O07427; -.
DR BRENDA; 3.1.1.23; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:MTBBASE.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0046503; P:glycerolipid catabolic process; IDA:MTBBASE.
DR GO; GO:0052151; P:positive regulation by symbiont of host apoptotic process; IDA:MTBBASE.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR022742; Hydrolase_4.
DR Pfam; PF12146; Hydrolase_4; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall; Hydrolase; Lipid degradation; Lipid metabolism;
KW Pharmaceutical; Reference proteome; Secreted; Virulence.
FT CHAIN 1..279
FT /note="Monoacylglycerol lipase"
FT /id="PRO_0000438237"
FT ACT_SITE 110
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:17784850,
FT ECO:0000305|PubMed:29895832"
FT ACT_SITE 226
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:17784850,
FT ECO:0000305|PubMed:29895832"
FT ACT_SITE 256
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:17784850,
FT ECO:0000305|PubMed:29895832"
FT MUTAGEN 110
FT /note="S->A: Loss of lipase activity."
FT /evidence="ECO:0000269|PubMed:17784850"
FT MUTAGEN 226
FT /note="D->A: Loss of lipase activity."
FT /evidence="ECO:0000269|PubMed:17784850"
FT MUTAGEN 256
FT /note="H->A: Loss of lipase activity."
FT /evidence="ECO:0000269|PubMed:17784850"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 17..27
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 30..36
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 47..55
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 81..98
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:6EIC"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 145..157
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 175..182
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 194..210
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 218..223
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 231..240
FT /evidence="ECO:0007829|PDB:6EIC"
FT STRAND 244..251
FT /evidence="ECO:0007829|PDB:6EIC"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:6EIC"
FT HELIX 264..276
FT /evidence="ECO:0007829|PDB:6EIC"
SQ SEQUENCE 279 AA; 30262 MW; 786557131F627E27 CRC64;
MTTTRTERNF AGIGDVRIVY DVWTPDTAPQ AVVVLAHGLG EHARRYDHVA QRLGAAGLVT
YALDHRGHGR SGGKRVLVRD ISEYTADFDT LVGIATREYP GCKRIVLGHS MGGGIVFAYG
VERPDNYDLM VLSAPAVAAQ DLVSPVVAVA AKLLGVVVPG LPVQELDFTA ISRDPEVVQA
YNTDPLVHHG RVPAGIGRAL LQVGETMPRR APALTAPLLV LHGTDDRLIP IEGSRRLVEC
VGSADVQLKE YPGLYHEVFN EPERNQVLDD VVAWLTERL
