LIPU_MYCTU
ID LIPU_MYCTU Reviewed; 297 AA.
AC O53424; I6Y5J0; L0T8J3;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 25-MAY-2022, entry version 116.
DE RecName: Full=Esterase LipU {ECO:0000305};
DE EC=3.1.1.- {ECO:0000269|PubMed:26398213, ECO:0000269|PubMed:28164792};
GN Name=lipU {ECO:0000312|EMBL:CCP43827.1};
GN OrderedLocusNames=Rv1076 {ECO:0000312|EMBL:CCP43827.1};
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 FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26398213; DOI=10.1371/journal.pone.0138151;
RA Cao J., Dang G., Li H., Li T., Yue Z., Li N., Liu Y., Liu S., Chen L.;
RT "Identification and characterization of lipase activity and immunogenicity
RT of LipL from Mycobacterium tuberculosis.";
RL PLoS ONE 10:E0138151-E0138151(2015).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, MUTAGENESIS OF SER-140; ASP-244 AND HIS-269, AND ACTIVE SITE.
RX PubMed=28164792; DOI=10.1016/j.micres.2016.12.005;
RA Li C., Li Q., Zhang Y., Gong Z., Ren S., Li P., Xie J.;
RT "Characterization and function of Mycobacterium tuberculosis H37Rv Lipase
RT Rv1076 (LipU).";
RL Microbiol. Res. 196:7-16(2017).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, MUTAGENESIS OF SER-140; GLU-239 AND HIS-269, AND ACTIVE SITE.
RX PubMed=28327423; DOI=10.1016/j.ijbiomac.2017.03.096;
RA Kaur G., Saini V., Kumari B., Kaur J., Kaur J.;
RT "Characterization of an extracellular protein, Rv1076 from M. tuberculosis
RT with a potential role in humoral response.";
RL Int. J. Biol. Macromol. 101:621-629(2017).
RN [5]
RP ACTIVITY REGULATION, AND IDENTIFICATION AS A DRUG TARGET.
RX PubMed=29557724; DOI=10.1080/07391102.2018.1454852;
RA Kaur G., Pandey B., Kumar A., Garewal N., Grover A., Kaur J.;
RT "Drug targeted virtual screening and molecular dynamics of LipU protein of
RT Mycobacterium tuberculosis and Mycobacterium leprae.";
RL J. Biomol. Struct. Dyn. 37:1254-1269(2019).
CC -!- FUNCTION: Esterase that shows preference for short chain fatty acids
CC (PubMed:26398213, PubMed:28164792, PubMed:28327423). Contributes to the
CC growth of M.tuberculosis during the nutritive stress (PubMed:28164792).
CC Elicits strong humoral response in both extrapulmonary and relapsed
CC cases of tuberculosis patients (PubMed:28327423).
CC {ECO:0000269|PubMed:26398213, ECO:0000269|PubMed:28164792,
CC ECO:0000269|PubMed:28327423}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acid ester + H2O = a fatty acid + an aliphatic alcohol
CC + H(+); Xref=Rhea:RHEA:59388, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:35748;
CC Evidence={ECO:0000269|PubMed:26398213, ECO:0000269|PubMed:28164792,
CC ECO:0000269|PubMed:28327423};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a butanoate ester + H2O = an aliphatic alcohol + butanoate +
CC H(+); Xref=Rhea:RHEA:47348, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:50477;
CC Evidence={ECO:0000269|PubMed:28164792, ECO:0000269|PubMed:28327423};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acetyl ester + H2O = acetate + an aliphatic alcohol + H(+);
CC Xref=Rhea:RHEA:12957, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:47622;
CC Evidence={ECO:0000269|PubMed:28164792, ECO:0000269|PubMed:28327423};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoate ester + H2O = an aliphatic alcohol + decanoate +
CC H(+); Xref=Rhea:RHEA:47360, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27689, ChEBI:CHEBI:87658;
CC Evidence={ECO:0000269|PubMed:28164792, ECO:0000269|PubMed:28327423};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an octanoate ester + H2O = an aliphatic alcohol + H(+) +
CC octanoate; Xref=Rhea:RHEA:47356, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:25646, ChEBI:CHEBI:87657;
CC Evidence={ECO:0000269|PubMed:28164792, ECO:0000269|PubMed:28327423};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dodecanoate ester + H2O = an aliphatic alcohol + dodecanoate
CC + H(+); Xref=Rhea:RHEA:47364, ChEBI:CHEBI:2571, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18262, ChEBI:CHEBI:87659;
CC Evidence={ECO:0000269|PubMed:28164792, ECO:0000269|PubMed:28327423};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoate ester = an aliphatic alcohol + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:47392, ChEBI:CHEBI:2571,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:25835; Evidence={ECO:0000269|PubMed:26398213};
CC -!- ACTIVITY REGULATION: Inhibited by the ionic detergent SDS and by the
CC serine protease inhibitor PMSF (PubMed:28164792). Inhibited by the FDA
CC approved drugs Diosmin, Acarbose and Ouabain. These drugs remain bound
CC in the active site pocket and could be probable drug candidates to
CC combat TB disease (PubMed:29557724). {ECO:0000269|PubMed:28164792,
CC ECO:0000269|PubMed:29557724}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.73 uM for pNP-butyrate {ECO:0000269|PubMed:28164792};
CC KM=333 uM for pNP-butyrate {ECO:0000269|PubMed:28327423};
CC Note=kcat is 49.8 min(-1) with pNP-butyrate as substrate.
CC {ECO:0000269|PubMed:28164792};
CC pH dependence:
CC Optimum pH is 8.0 (with pNP-butyrate as substrate).
CC {ECO:0000269|PubMed:28164792, ECO:0000269|PubMed:28327423};
CC Temperature dependence:
CC Optimum temperature is 40 degrees Celsius (with pNP-butyrate as
CC substrate). {ECO:0000269|PubMed:28164792,
CC ECO:0000269|PubMed:28327423};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28327423}.
CC Note=Extracellular. {ECO:0000269|PubMed:28327423}.
CC -!- INDUCTION: Up-regulated in nutritive stress but not in acidic and
CC oxidative stress. {ECO:0000269|PubMed:28164792}.
CC -!- MISCELLANEOUS: Was identified as a drug target.
CC {ECO:0000269|PubMed:29557724}.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43827.1; -; Genomic_DNA.
DR RefSeq; NP_215592.1; NC_000962.3.
DR RefSeq; WP_003900268.1; NC_000962.3.
DR AlphaFoldDB; O53424; -.
DR SMR; O53424; -.
DR STRING; 83332.Rv1076; -.
DR SwissLipids; SLP:000001358; -.
DR ESTHER; myctu-Rv1076; Hormone-sensitive_lipase_like.
DR PaxDb; O53424; -.
DR DNASU; 887112; -.
DR GeneID; 45425048; -.
DR GeneID; 887112; -.
DR KEGG; mtu:Rv1076; -.
DR PATRIC; fig|83332.111.peg.1198; -.
DR TubercuList; Rv1076; -.
DR eggNOG; COG0657; Bacteria.
DR OMA; RVWPGQI; -.
DR PhylomeDB; O53424; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008126; F:acetylesterase activity; IEA:RHEA.
DR GO; GO:0004806; F:triglyceride lipase activity; IBA:GO_Central.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR033140; Lipase_GDXG_put_SER_AS.
DR Pfam; PF07859; Abhydrolase_3; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS01174; LIPASE_GDXG_SER; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Reference proteome; Secreted.
FT CHAIN 1..297
FT /note="Esterase LipU"
FT /id="PRO_0000448882"
FT ACT_SITE 140
FT /evidence="ECO:0000305|PubMed:28164792,
FT ECO:0000305|PubMed:28327423"
FT ACT_SITE 239
FT /evidence="ECO:0000305|PubMed:28327423"
FT ACT_SITE 269
FT /evidence="ECO:0000305|PubMed:28164792,
FT ECO:0000305|PubMed:28327423"
FT MUTAGEN 140
FT /note="S->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:28164792,
FT ECO:0000269|PubMed:28327423"
FT MUTAGEN 239
FT /note="E->A: 85% loss of activity."
FT /evidence="ECO:0000269|PubMed:28327423"
FT MUTAGEN 244
FT /note="D->A: 20% loss of activity."
FT /evidence="ECO:0000269|PubMed:28164792"
FT MUTAGEN 269
FT /note="H->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:28164792,
FT ECO:0000269|PubMed:28327423"
SQ SEQUENCE 297 AA; 31681 MW; 400FF66FEC76AEE5 CRC64;
MAVRPVLAVG SYLPHAPWPW GVIDQAARVL LPASTTVRAA VSLPNASAQL VRASGVLPAD
GTRRAVLYLH GGAFLTCGAN SHGRLVELLS KFADSPVLVV DYRLIPKHSI GMALDDCHDG
YRWLRLLGYE PEQIVLAGDS AGGYLALALA QRLQEVGEEP AALVAISPLL QLAKEHKQAH
PNIKTDAMFP ARAFDALDAL VASAAARNQV DGEPEELYEP LEHITPGLPR TLIHVSGSEV
LLHDAQLAAA KLAAAGVPAE VRVWPGQVHD FQVAASMLPE AIRSLRQIGE YIREATG
