TRES_MYCTU
ID TRES_MYCTU Reviewed; 601 AA.
AC P9WQ19; L0T5R2; O07176; Q7DAF7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=Trehalose synthase/amylase TreS {ECO:0000303|PubMed:18505459};
DE EC=3.2.1.1 {ECO:0000269|PubMed:18505459};
DE EC=5.4.99.16 {ECO:0000269|PubMed:18505459};
DE AltName: Full=Maltose alpha-D-glucosyltransferase {ECO:0000303|PubMed:18505459};
DE Short=MTase {ECO:0000303|PubMed:18505459};
GN Name=treS {ECO:0000303|PubMed:18505459}; OrderedLocusNames=Rv0126;
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 AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP FUNCTION AS A TREHALOSE SYNTHASE AND AMYLASE, AND CATALYTIC ACTIVITY.
RX PubMed=18505459; DOI=10.1111/j.1742-4658.2008.06491.x;
RA Pan Y.T., Carroll J.D., Asano N., Pastuszak I., Edavana V.K., Elbein A.D.;
RT "Trehalose synthase converts glycogen to trehalose.";
RL FEBS J. 275:3408-3420(2008).
RN [4]
RP DISRUPTION PHENOTYPE, AND SYNTHETIC LETHALITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20305657; DOI=10.1038/nchembio.340;
RA Kalscheuer R., Syson K., Veeraraghavan U., Weinrick B., Biermann K.E.,
RA Liu Z., Sacchettini J.C., Besra G., Bornemann S., Jacobs W.R. Jr.;
RT "Self-poisoning of Mycobacterium tuberculosis by targeting GlgE in an
RT alpha-glucan pathway.";
RL Nat. Chem. Biol. 6:376-384(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, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=27513637; DOI=10.1371/journal.ppat.1005768;
RA Koliwer-Brandl H., Syson K., van de Weerd R., Chandra G., Appelmelk B.,
RA Alber M., Ioerger T.R., Jacobs W.R. Jr., Geurtsen J., Bornemann S.,
RA Kalscheuer R.;
RT "Metabolic network for the biosynthesis of intra- and extracellular alpha-
RT glucans required for virulence of Mycobacterium tuberculosis.";
RL PLoS Pathog. 12:E1005768-E1005768(2016).
CC -!- FUNCTION: Catalyzes the reversible interconversion of maltose and
CC trehalose by transglucosylation (PubMed:18505459). Also displays
CC amylase activity, catalyzing the endohydrolysis of (1->4)-alpha-D-
CC glucosidic linkages in glycogen and maltooligosaccharides such as
CC maltoheptaose, to produce maltose which then can be converted to
CC trehalose (PubMed:18505459). TreS plays a key role in the utilization
CC of trehalose for the production of glycogen and alpha-glucan via the
CC TreS-Pep2 branch involved in the biosynthesis of maltose-1-phosphate
CC (M1P) (PubMed:18505459, PubMed:27513637). Might also function as a
CC sensor and/or regulator of trehalose levels within the cell
CC (PubMed:18505459). Thus, when trehalose levels in the cell become
CC dangerously low, TreS could expedite the conversion of glycogen to
CC maltose via its amylase activity and then convert the maltose to
CC trehalose; but this enzyme also could expedite or promote the
CC conversion of trehalose to glycogen when cytoplasmic trehalose levels
CC become too high (PubMed:18505459). {ECO:0000269|PubMed:18505459,
CC ECO:0000269|PubMed:27513637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-maltose = alpha,alpha-trehalose; Xref=Rhea:RHEA:15145,
CC ChEBI:CHEBI:16551, ChEBI:CHEBI:17306; EC=5.4.99.16;
CC Evidence={ECO:0000269|PubMed:18505459};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Endohydrolysis of (1->4)-alpha-D-glucosidic linkages in
CC polysaccharides containing three or more (1->4)-alpha-linked D-
CC glucose units.; EC=3.2.1.1; Evidence={ECO:0000269|PubMed:18505459};
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC {ECO:0000269|PubMed:27513637}.
CC -!- PATHWAY: Capsule biogenesis; capsule polysaccharide biosynthesis.
CC {ECO:0000269|PubMed:27513637}.
CC -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:A0R6E0}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are as virulent as wild-
CC type in mice, however also show a profound impact on intracellular and
CC capsular glucan (PubMed:20305657, PubMed:27513637). It is not possible
CC to inactivate Rv3032 in a mutant lacking treS, suggesting the joint
CC essentiality of the different alpha-(1->4)-glucans biosynthesis
CC pathways involving these two genes (PubMed:20305657). Combined
CC inactivation of glgM and treS results in absence of alpha-glucan
CC (PubMed:27513637). Combined inactivation of treS and glgC results in
CC absence of alpha-glucan content and is significantly attenuated for
CC growth in the lung and spleen of BALB/C mice during both the acute and
CC chronic phase of infection (PubMed:27513637).
CC {ECO:0000269|PubMed:20305657, ECO:0000269|PubMed:27513637}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- MISCELLANEOUS: Maltose-1-phosphate (M1P), the building block required
CC for alpha-glucan production, is generated by two alternative routes:
CC the TreS-Pep2 branch and the GlgC-GlgM branch, however it seems that
CC TreS-Pep2 branch provides most of M1P for the GlgE pathway in
CC M.tuberculosis. {ECO:0000269|PubMed:27513637}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 13 family. TreS
CC subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP42851.1; -; Genomic_DNA.
DR PIR; G70983; G70983.
DR RefSeq; NP_214640.1; NC_000962.3.
DR RefSeq; WP_003400893.1; NZ_NVQJ01000001.1.
DR AlphaFoldDB; P9WQ19; -.
DR SMR; P9WQ19; -.
DR STRING; 83332.Rv0126; -.
DR PaxDb; P9WQ19; -.
DR GeneID; 45424092; -.
DR GeneID; 886881; -.
DR KEGG; mtu:Rv0126; -.
DR TubercuList; Rv0126; -.
DR eggNOG; COG0366; Bacteria.
DR OMA; PNGEKWA; -.
DR PhylomeDB; P9WQ19; -.
DR BRENDA; 5.4.99.16; 3445.
DR Reactome; R-MTU-868688; Trehalose biosynthesis.
DR UniPathway; UPA00164; -.
DR UniPathway; UPA00934; -.
DR PHI-base; PHI:6732; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004556; F:alpha-amylase activity; ISS:UniProtKB.
DR GO; GO:0016161; F:beta-amylase activity; IDA:MTBBASE.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0047471; F:maltose alpha-D-glucosyltransferase activity; IDA:MTBBASE.
DR GO; GO:0045227; P:capsule polysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0005978; P:glycogen biosynthetic process; IMP:MTBBASE.
DR GO; GO:0005977; P:glycogen metabolic process; ISS:UniProtKB.
DR GO; GO:0000023; P:maltose metabolic process; ISS:UniProtKB.
DR GO; GO:0000272; P:polysaccharide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0005992; P:trehalose biosynthetic process; IMP:MTBBASE.
DR GO; GO:0005991; P:trehalose metabolic process; ISS:UniProtKB.
DR Gene3D; 2.60.40.1180; -; 1.
DR Gene3D; 3.90.400.10; -; 1.
DR InterPro; IPR006047; Glyco_hydro_13_cat_dom.
DR InterPro; IPR013780; Glyco_hydro_b.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR032091; Malt_amylase_C.
DR InterPro; IPR045857; O16G_dom_2.
DR InterPro; IPR012810; TreS/a-amylase_N.
DR Pfam; PF00128; Alpha-amylase; 1.
DR Pfam; PF16657; Malt_amylase_C; 1.
DR SMART; SM00642; Aamy; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR TIGRFAMs; TIGR02456; treS_nterm; 1.
PE 1: Evidence at protein level;
KW Calcium; Capsule biogenesis/degradation; Carbohydrate metabolism;
KW Glycogen biosynthesis; Glycogen metabolism; Glycosidase; Hydrolase;
KW Isomerase; Metal-binding; Polysaccharide degradation; Reference proteome.
FT CHAIN 1..601
FT /note="Trehalose synthase/amylase TreS"
FT /id="PRO_0000412906"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 238
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:A0R6E0"
FT ACT_SITE 280
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
FT BINDING 140
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0R6E0"
FT BINDING 141
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
FT BINDING 206
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0R6E0"
FT BINDING 236
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
FT BINDING 242
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0R6E0"
FT BINDING 243
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0R6E0"
FT BINDING 245
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:A0R6E0"
FT BINDING 349
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
FT BINDING 350
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9ZEU2"
SQ SEQUENCE 601 AA; 68593 MW; FE52E5258F38116E CRC64;
MNEAEHSVEH PPVQGSHVEG GVVEHPDAKD FGSAAALPAD PTWFKHAVFY EVLVRAFFDA
SADGSGDLRG LIDRLDYLQW LGIDCIWLPP FYDSPLRDGG YDIRDFYKVL PEFGTVDDFV
ALVDAAHRRG IRIITDLVMN HTSESHPWFQ ESRRDPDGPY GDYYVWSDTS ERYTDARIIF
VDTEESNWSF DPVRRQFYWH RFFSHQPDLN YDNPAVQEAM IDVIRFWLGL GIDGFRLDAV
PYLFEREGTN CENLPETHAF LKRVRKVVDD EFPGRVLLAE ANQWPGDVVE YFGDPNTGGD
ECHMAFHFPL MPRIFMAVRR ESRFPISEII AQTPPIPDMA QWGIFLRNHD ELTLEMVTDE
ERDYMYAEYA KDPRMKANVG IRRRLAPLLD NDRNQIELFT ALLLSLPGSP VLYYGDEIGM
GDVIWLGDRD GVRIPMQWTP DRNAGFSTAN PGRLYLPPSQ DPVYGYQAVN VEAQRDTSTS
LLNFTRTMLA VRRRHPAFAV GAFQELGGSN PSVLAYVRQV AGDDGDTVLC VNNLSRFPQP
IELDLQQWTN YTPVELTGHV EFPRIGQVPY LLTLPGHGFY WFQLTTHEVG APPTCGGERR
L
