OTSB_MYCTU
ID OTSB_MYCTU Reviewed; 391 AA.
AC P9WFZ5; L0TCC3; O50401; Q7D5L8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Trehalose-phosphate phosphatase;
DE Short=TPP;
DE EC=3.1.3.12;
DE AltName: Full=Trehalose-6-phosphate phosphatase;
GN Name=otsB; Synonyms=otsB2; OrderedLocusNames=Rv3372;
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, ACTIVITY REGULATION, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15158675; DOI=10.1016/j.abb.2004.02.014;
RA Edavana V.K., Pastuszak I., Carroll J.D., Thampi P., Abraham E.C.,
RA Elbein A.D.;
RT "Cloning and expression of the trehalose-phosphate phosphatase of
RT Mycobacterium tuberculosis: comparison to the enzyme from Mycobacterium
RT smegmatis.";
RL Arch. Biochem. Biophys. 426:250-257(2004).
RN [3]
RP FUNCTION IN TREHALOSE BIOSYNTHESIS, ACTIVITY REGULATION, COFACTOR, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15703182; DOI=10.1074/jbc.m414232200;
RA Murphy H.N., Stewart G.R., Mischenko V.V., Apt A.S., Harris R.,
RA McAlister M.S.B., Driscoll P.C., Young D.B., Robertson B.D.;
RT "The OtsAB pathway is essential for trehalose biosynthesis in Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 280:14524-14529(2005).
RN [4]
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 [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).
CC -!- FUNCTION: Removes the phosphate from trehalose 6-phosphate to produce
CC free trehalose. {ECO:0000269|PubMed:15158675,
CC ECO:0000269|PubMed:15703182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha,alpha-trehalose 6-phosphate + H2O = alpha,alpha-
CC trehalose + phosphate; Xref=Rhea:RHEA:23420, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16551, ChEBI:CHEBI:43474, ChEBI:CHEBI:58429; EC=3.1.3.12;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15158675, ECO:0000269|PubMed:15703182};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15158675, ECO:0000269|PubMed:15703182};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and calcium. Diumycin and
CC moenomycin stimulate activity at concentrations of up to 100 ug/ml, and
CC then inhibit at higher concentrations. {ECO:0000269|PubMed:15158675,
CC ECO:0000269|PubMed:15703182}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 mM for trehalose-6-phosphate (at 37 degrees Celsius and pH
CC 7.5) {ECO:0000269|PubMed:15158675, ECO:0000269|PubMed:15703182};
CC KM=0.6 mM for trehalose-6-phosphate (at 37 degrees Celsius and pH
CC 7.0) {ECO:0000269|PubMed:15158675, ECO:0000269|PubMed:15703182};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:15158675,
CC ECO:0000269|PubMed:15703182};
CC Temperature dependence:
CC Thermostable at 50 degrees Celsius for at least 5 minutes.
CC {ECO:0000269|PubMed:15158675, ECO:0000269|PubMed:15703182};
CC -!- PATHWAY: Glycan biosynthesis; trehalose biosynthesis.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the trehalose phosphatase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46193.1; -; Genomic_DNA.
DR PIR; C70972; C70972.
DR RefSeq; NP_217889.1; NC_000962.3.
DR RefSeq; WP_003417892.1; NZ_NVQJ01000052.1.
DR PDB; 5GVX; X-ray; 2.60 A; A=2-391.
DR PDBsum; 5GVX; -.
DR AlphaFoldDB; P9WFZ5; -.
DR SMR; P9WFZ5; -.
DR STRING; 83332.Rv3372; -.
DR PaxDb; P9WFZ5; -.
DR DNASU; 888137; -.
DR GeneID; 888137; -.
DR KEGG; mtu:Rv3372; -.
DR TubercuList; Rv3372; -.
DR eggNOG; COG0561; Bacteria.
DR eggNOG; COG0637; Bacteria.
DR OMA; HKLAKHP; -.
DR PhylomeDB; P9WFZ5; -.
DR BRENDA; 3.1.3.12; 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:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0004805; F:trehalose-phosphatase activity; IDA:MTBBASE.
DR GO; GO:0016311; P:dephosphorylation; IMP:UniProtKB.
DR GO; GO:0005992; P:trehalose biosynthetic process; IDA:MTBBASE.
DR Gene3D; 3.40.50.1000; -; 2.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR006379; HAD-SF_hydro_IIB.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR044651; OTSB-like.
DR InterPro; IPR003337; Trehalose_PPase.
DR PANTHER; PTHR43768; PTHR43768; 1.
DR Pfam; PF02358; Trehalose_PPase; 1.
DR SUPFAM; SSF56784; SSF56784; 2.
DR TIGRFAMs; TIGR01484; HAD-SF-IIB; 1.
DR TIGRFAMs; TIGR00685; T6PP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Reference proteome.
FT CHAIN 1..391
FT /note="Trehalose-phosphate phosphatase"
FT /id="PRO_0000370706"
FT ACT_SITE 147
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 147..149
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 147
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 149
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:5GVX"
FT TURN 11..13
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 15..20
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 27..35
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 50..55
FT /evidence="ECO:0007829|PDB:5GVX"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 71..79
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 103..108
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 127..131
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 142..147
FT /evidence="ECO:0007829|PDB:5GVX"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 168..176
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 189..196
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 200..205
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 222..225
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 228..242
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 249..253
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:5GVX"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 269..283
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 304..313
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 335..338
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 346..350
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:5GVX"
FT STRAND 363..368
FT /evidence="ECO:0007829|PDB:5GVX"
FT HELIX 369..385
FT /evidence="ECO:0007829|PDB:5GVX"
SQ SEQUENCE 391 AA; 41720 MW; 87AAC490926F9187 CRC64;
MRKLGPVTID PRRHDAVLFD TTLDATQELV RQLQEVGVGT GVFGSGLDVP IVAAGRLAVR
PGRCVVVSAH SAGVTAARES GFALIIGVDR TGCRDALRRD GADTVVTDLS EVSVRTGDRR
MSQLPDALQA LGLADGLVAR QPAVFFDFDG TLSDIVEDPD AAWLAPGALE ALQKLAARCP
IAVLSGRDLA DVTQRVGLPG IWYAGSHGFE LTAPDGTHHQ NDAAAAAIPV LKQAAAELRQ
QLGPFPGVVV EHKRFGVAVH YRNAARDRVG EVAAAVRTAE QRHALRVTTG REVIELRPDV
DWDKGKTLLW VLDHLPHSGS APLVPIYLGD DITDEDAFDV VGPHGVPIVV RHTDDGDRAT
AALFALDSPA RVAEFTDRLA RQLREAPLRA T
