TESA_MYCTU
ID TESA_MYCTU Reviewed; 261 AA.
AC P9WQD5; L0TBA2; P63460; Q10974;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Thioesterase TesA {ECO:0000303|PubMed:30292819, ECO:0000303|PubMed:31388991};
DE EC=3.1.2.- {ECO:0000269|PubMed:30292819, ECO:0000269|PubMed:31388991};
DE AltName: Full=Acetylesterase {ECO:0000305};
DE EC=3.1.1.6 {ECO:0000269|PubMed:30292819};
DE AltName: Full=Palmitoyl-CoA hydrolase {ECO:0000305};
DE EC=3.1.2.2 {ECO:0000269|PubMed:30292819, ECO:0000269|PubMed:31388991};
GN Name=tesA {ECO:0000303|PubMed:30292819}; OrderedLocusNames=Rv2928;
GN ORFNames=MTCY338.17;
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 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 [3]
RP INTERACTION WITH PPSE.
RC STRAIN=H37Rv;
RX PubMed=15668773; DOI=10.1007/s00438-004-1088-3;
RA Rao A., Ranganathan A.;
RT "Interaction studies on proteins encoded by the phthiocerol dimycocerosate
RT locus of Mycobacterium tuberculosis.";
RL Mol. Genet. Genomics 272:571-579(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=31388991; DOI=10.1002/1873-3468.13555;
RA Yang D., Vandenbussche G., Vertommen D., Evrard D., Abskharon R.,
RA Cavalier J.F., Berger G., Canaan S., Khan M.S., Zeng S., Wohlkoenig A.,
RA Prevost M., Soumillion P., Fontaine V.;
RT "Methyl arachidonyl fluorophosphonate inhibits Mycobacterium tuberculosis
RT thioesterase TesA and globally affects vancomycin susceptibility.";
RL FEBS Lett. 594:79-93(2020).
RN [5] {ECO:0007744|PDB:6FVJ, ECO:0007744|PDB:6FW5}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP CYC17 INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACTIVE
RP SITE, AND MUTAGENESIS OF SER-104.
RC STRAIN=H37Rv;
RX PubMed=30292819; DOI=10.1016/j.jmb.2018.09.017;
RA Nguyen P.C., Nguyen V.S., Martin B.P., Fourquet P., Camoin L.,
RA Spilling C.D., Cavalier J.F., Cambillau C., Canaan S.;
RT "Biochemical and structural characterization of TesA, a major thioesterase
RT required for outer-envelope lipid biosynthesis in Mycobacterium
RT tuberculosis.";
RL J. Mol. Biol. 430:5120-5136(2018).
CC -!- FUNCTION: Involved in the synthesis of both phthiocerol dimycocerosates
CC (PDIMs) and phenolic glycolipids (PGLs), which are structurally related
CC lipids non-covalently bound to the outer cell wall layer of
CC M.tuberculosis and are important virulence factors (PubMed:30292819).
CC In vitro, TesA has both thioesterase and esterase activities
CC (PubMed:30292819, PubMed:31388991). Exhibits thioesterase activity on
CC acyl-CoA derivatives such as palmitoyl-CoA and decanoyl-CoA
CC (PubMed:30292819, PubMed:31388991). Also displays hydrolytic activity
CC on ester substrates, being more active on pNP esters with short carbon
CC chain lengths (C2-C5) than with those bearing medium and long carbon
CC chain lengths (C8-C18) (PubMed:30292819). {ECO:0000269|PubMed:30292819,
CC ECO:0000269|PubMed:31388991}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-CoA + H2O = a fatty acid + CoA + H(+);
CC Xref=Rhea:RHEA:16781, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:57287, ChEBI:CHEBI:77636;
CC Evidence={ECO:0000269|PubMed:31388991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoyl-CoA = CoA + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:16645, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379; EC=3.1.2.2;
CC Evidence={ECO:0000269|PubMed:30292819, ECO:0000269|PubMed:31388991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + H2O = CoA + decanoate + H(+);
CC Xref=Rhea:RHEA:40059, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:27689, ChEBI:CHEBI:57287, ChEBI:CHEBI:61430;
CC Evidence={ECO:0000269|PubMed:31388991};
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; EC=3.1.1.6;
CC Evidence={ECO:0000269|PubMed:30292819};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + pentanoate ester = an aliphatic alcohol + H(+) +
CC pentanoate; Xref=Rhea:RHEA:48436, ChEBI:CHEBI:2571,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:31011,
CC ChEBI:CHEBI:50871; Evidence={ECO:0000269|PubMed:30292819};
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:30292819};
CC -!- ACTIVITY REGULATION: Strongly inhibited in vitro by CyC17, a monocyclic
CC enol phosphate analog to Cyclipostins, which binds covalently to the
CC catalytic Ser-104 residue leading to a total loss of enzyme activity
CC (PubMed:30292819). Methyl arachidonyl fluorophosphonate (MAFP) inhibits
CC esterase activity but it only reduces by approximately 50% thioesterase
CC activity with palmitoyl-CoA as substrate (PubMed:31388991).
CC Thioesterase activity is inhibited by tetrahydrolipstatin (THL)
CC (PubMed:31388991). {ECO:0000269|PubMed:30292819,
CC ECO:0000269|PubMed:31388991}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=57.44 uM for palmitoyl-CoA {ECO:0000269|PubMed:31388991};
CC Note=kcat is 0.00342 sec(-1) with palmitoyl-CoA as substrate.
CC {ECO:0000269|PubMed:31388991};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius (with palmitoyl-CoA as
CC substrate). {ECO:0000269|PubMed:31388991};
CC -!- SUBUNIT: Monomer. Can form homodimers in the presence of palmitoyl-CoA
CC (PubMed:31388991). Interacts with the C-terminal region of PpsE
CC (PubMed:15668773). {ECO:0000269|PubMed:15668773,
CC ECO:0000269|PubMed:31388991}.
CC -!- SIMILARITY: Belongs to the thioesterase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45731.1; -; Genomic_DNA.
DR PIR; H70748; H70748.
DR RefSeq; NP_217444.1; NC_000962.3.
DR RefSeq; WP_003414828.1; NZ_NVQJ01000006.1.
DR PDB; 6FVJ; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-261.
DR PDB; 6FW5; X-ray; 2.75 A; A/B/C/D=1-261.
DR PDBsum; 6FVJ; -.
DR PDBsum; 6FW5; -.
DR AlphaFoldDB; P9WQD5; -.
DR SMR; P9WQD5; -.
DR STRING; 83332.Rv2928; -.
DR SwissLipids; SLP:000001933; -.
DR ESTHER; myctu-yt28; Thioesterase.
DR PaxDb; P9WQD5; -.
DR DNASU; 887446; -.
DR GeneID; 887446; -.
DR KEGG; mtu:Rv2928; -.
DR TubercuList; Rv2928; -.
DR eggNOG; COG3208; Bacteria.
DR OMA; FIHDEVE; -.
DR PhylomeDB; P9WQD5; -.
DR BioCyc; MetaCyc:G185E-7181-MON; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008126; F:acetylesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0102991; F:myristoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0016290; F:palmitoyl-CoA hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0071770; P:DIM/DIP cell wall layer assembly; IMP:MTBBASE.
DR GO; GO:0008610; P:lipid biosynthetic process; IMP:MTBBASE.
DR GO; GO:0052562; P:suppression by symbiont of host immune response; IDA:MTBBASE.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR020802; PKS_thioesterase.
DR InterPro; IPR012223; TEII.
DR InterPro; IPR001031; Thioesterase.
DR PANTHER; PTHR11487; PTHR11487; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00824; PKS_TE; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Lipid biosynthesis; Lipid metabolism;
KW Reference proteome; Virulence.
FT CHAIN 1..261
FT /note="Thioesterase TesA"
FT /id="PRO_0000180368"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 104
FT /evidence="ECO:0000305|PubMed:30292819"
FT ACT_SITE 208
FT /evidence="ECO:0000305|PubMed:30292819"
FT ACT_SITE 236
FT /evidence="ECO:0000305|PubMed:30292819"
FT MUTAGEN 104
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:30292819"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 45..49
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 77..88
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 105..119
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 123..131
FT /evidence="ECO:0007829|PDB:6FVJ"
FT TURN 141..144
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 150..153
FT /evidence="ECO:0007829|PDB:6FVJ"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 200..205
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 213..216
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 217..222
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:6FVJ"
FT STRAND 227..235
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:6FVJ"
FT HELIX 243..257
FT /evidence="ECO:0007829|PDB:6FVJ"
SQ SEQUENCE 261 AA; 29152 MW; 49FA9B32D8C636C2 CRC64;
MLARHGPRYG GSVNGHSDDS SGDAKQAAPT LYIFPHAGGT AKDYVAFSRE FSADVKRIAV
QYPGQHDRSG LPPLESIPTL ADEIFAMMKP SARIDDPVAF FGHSMGGMLA FEVALRYQSA
GHRVLAFFVS ACSAPGHIRY KQLQDLSDRE MLDLFTRMTG MNPDFFTDDE FFVGALPTLR
AVRAIAGYSC PPETKLSCPI YAFIGDKDWI ATQDDMDPWR DRTTEEFSIR VFPGDHFYLN
DNLPELVSDI EDKTLQWHDR A
