OTSA_MYCTU
ID OTSA_MYCTU Reviewed; 500 AA.
AC P9WN11; L0TE99; O06353; Q7D5F6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Trehalose-6-phosphate synthase {ECO:0000303|PubMed:12473104};
DE Short=TPS {ECO:0000303|PubMed:12473104};
DE EC=2.4.1.15 {ECO:0000269|PubMed:12473104};
DE EC=2.4.1.347 {ECO:0000269|PubMed:12473104};
DE AltName: Full=Alpha,alpha-trehalose-phosphate synthase [UDP-forming] {ECO:0000305};
DE AltName: Full=Osmoregulatory trehalose synthesis protein A {ECO:0000250|UniProtKB:P31677};
DE Short=OtsA {ECO:0000250|UniProtKB:P31677};
GN Name=otsA {ECO:0000303|PubMed:12473104}; OrderedLocusNames=Rv3490;
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, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12473104; DOI=10.1046/j.1432-1033.2002.03327.x;
RA Pan Y.T., Carroll J.D., Elbein A.D.;
RT "Trehalose-phosphate synthase of Mycobacterium tuberculosis. Cloning,
RT expression and properties of the recombinant enzyme.";
RL Eur. J. Biochem. 269:6091-6100(2002).
RN [3]
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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: Involved in the production of glycogen and alpha-glucan via
CC the TreS-Pep2 branch involved in the biosynthesis of maltose-1-
CC phosphate (M1P), and probably in the osmoprotection via the
CC biosynthesis of trehalose (PubMed:12473104, PubMed:27513637). Catalyzes
CC the transfer of glucose from UDP-glucose (UDP-Glc) to D-glucose 6-
CC phosphate (Glc-6-P) to form trehalose-6-phosphate (PubMed:12473104). Is
CC specific for the glucosyl acceptor (Glc-6-P cannot be replaced by
CC either mannose-6-P, fructose-6-P or glucosamine-6-P), but any of the
CC glucose sugar nucleotides can be used as glucosyl donors
CC (PubMed:12473104). It is more active with the purine sugar nucleotides
CC than with the pyrimidine sugar nucleotides (PubMed:12473104).
CC {ECO:0000269|PubMed:12473104, ECO:0000269|PubMed:27513637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-alpha-D-glucose + D-glucose 6-phosphate = ADP +
CC alpha,alpha-trehalose 6-phosphate + H(+); Xref=Rhea:RHEA:53880,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57498, ChEBI:CHEBI:58429,
CC ChEBI:CHEBI:61548, ChEBI:CHEBI:456216; EC=2.4.1.347;
CC Evidence={ECO:0000269|PubMed:12473104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CDP-alpha-D-glucose + D-glucose 6-phosphate = alpha,alpha-
CC trehalose 6-phosphate + CDP + H(+); Xref=Rhea:RHEA:53884,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58069, ChEBI:CHEBI:58429,
CC ChEBI:CHEBI:61548, ChEBI:CHEBI:137927;
CC Evidence={ECO:0000269|PubMed:12473104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + GDP-alpha-D-glucose = alpha,alpha-
CC trehalose 6-phosphate + GDP + H(+); Xref=Rhea:RHEA:14605,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58189, ChEBI:CHEBI:58429,
CC ChEBI:CHEBI:61548, ChEBI:CHEBI:62230;
CC Evidence={ECO:0000269|PubMed:12473104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + TDP-alpha-D-glucose = alpha,alpha-
CC trehalose 6-phosphate + H(+) + TDP; Xref=Rhea:RHEA:53888,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58429, ChEBI:CHEBI:61417,
CC ChEBI:CHEBI:61548, ChEBI:CHEBI:137931;
CC Evidence={ECO:0000269|PubMed:12473104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + UDP-alpha-D-glucose = alpha,alpha-
CC trehalose 6-phosphate + H(+) + UDP; Xref=Rhea:RHEA:18889,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58429,
CC ChEBI:CHEBI:58885, ChEBI:CHEBI:61548; EC=2.4.1.15;
CC Evidence={ECO:0000269|PubMed:12473104};
CC -!- ACTIVITY REGULATION: Activity is increased about twofold by 10 mM
CC manganese. ADP, at 10 mM concentration, inhibits the formation of
CC trehalose-P by 70% with either UDP-glucose or GDP-glucose as substrate,
CC but GDP, also at 10 mM, only inhibits the reaction with UDP-glucose
CC (50%) but not with GDP-glucose. {ECO:0000269|PubMed:12473104}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=18 mM for UDP-glucose {ECO:0000269|PubMed:12473104};
CC KM=16 mM for GDP-glucose {ECO:0000269|PubMed:12473104};
CC KM=7 mM for D-glucose 6-phosphate (with UDP-glucose as glucosyl
CC donor) {ECO:0000269|PubMed:12473104};
CC KM=4 mM for D-glucose 6-phosphate (with GDP-glucose as glucosyl
CC donor) {ECO:0000269|PubMed:12473104};
CC -!- PATHWAY: Glycan biosynthesis; trehalose biosynthesis. {ECO:0000305}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:12473104}.
CC -!- DISRUPTION PHENOTYPE: Combined inactivation of both glgM and ostA is
CC lethal, potentially due to accumulation of toxic levels of ADP-glucose.
CC Combined inactivation of otsA and glgC results in a loss of alpha-
CC glucans and maltose-1-phosphate (M1P). {ECO:0000269|PubMed:27513637}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 20 family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP46312.1; -; Genomic_DNA.
DR PIR; G70569; G70569.
DR RefSeq; NP_218007.1; NC_000962.3.
DR RefSeq; WP_003900868.1; NZ_NVQJ01000042.1.
DR AlphaFoldDB; P9WN11; -.
DR SMR; P9WN11; -.
DR STRING; 83332.Rv3490; -.
DR PaxDb; P9WN11; -.
DR DNASU; 888404; -.
DR GeneID; 888404; -.
DR KEGG; mtu:Rv3490; -.
DR TubercuList; Rv3490; -.
DR eggNOG; COG0380; Bacteria.
DR OMA; YYGFSNR; -.
DR PhylomeDB; P9WN11; -.
DR BioCyc; MetaCyc:G185E-7767-MON; -.
DR BRENDA; 2.4.1.347; 3445.
DR Reactome; R-MTU-868688; Trehalose biosynthesis.
DR UniPathway; UPA00299; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0047260; F:alpha,alpha-trehalose-phosphate synthase (GDP-forming) activity; IDA:MTBBASE.
DR GO; GO:0003825; F:alpha,alpha-trehalose-phosphate synthase (UDP-forming) activity; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0005992; P:trehalose biosynthetic process; IDA:MTBBASE.
DR CDD; cd03788; GT20_TPS; 1.
DR InterPro; IPR001830; Glyco_trans_20.
DR PANTHER; PTHR10788; PTHR10788; 1.
DR Pfam; PF00982; Glyco_transf_20; 1.
PE 1: Evidence at protein level;
KW Glycosyltransferase; Reference proteome; Transferase.
FT CHAIN 1..500
FT /note="Trehalose-6-phosphate synthase"
FT /id="PRO_0000348922"
FT BINDING 28
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 48..49
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 108
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 162
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 304
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 309
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 342
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT BINDING 407..411
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT SITE 117
FT /note="Involved in alpha anomer selectivity"
FT /evidence="ECO:0000250|UniProtKB:P31677"
FT SITE 187
FT /note="Involved in alpha anomer selectivity"
FT /evidence="ECO:0000250|UniProtKB:P31677"
SQ SEQUENCE 500 AA; 55862 MW; 5200FA01BB77CA8D CRC64;
MAPSGGQEAQ ICDSETFGDS DFVVVANRLP VDLERLPDGS TTWKRSPGGL VTALEPVLRR
RRGAWVGWPG VNDDGAEPDL HVLDGPIIQD ELELHPVRLS TTDIAQYYEG FSNATLWPLY
HDVIVKPLYH REWWDRYVDV NQRFAEAASR AAAHGATVWV QDYQLQLVPK MLRMLRPDLT
IGFFLHIPFP PVELFMQMPW RTEIIQGLLG ADLVGFHLPG GAQNFLILSR RLVGTDTSRG
TVGVRSRFGA AVLGSRTIRV GAFPISVDSG ALDHAARDRN IRRRAREIRT ELGNPRKILL
GVDRLDYTKG IDVRLKAFSE LLAEGRVKRD DTVVVQLATP SRERVESYQT LRNDIERQVG
HINGEYGEVG HPVVHYLHRP APRDELIAFF VASDVMLVTP LRDGMNLVAK EYVACRSDLG
GALVLSEFTG AAAELRHAYL VNPHDLEGVK DGIEEALNQT EEAGRRRMRS LRRQVLAHDV
DRWAQSFLDA LAGAHPRGQG
