THIE_MYCTU
ID THIE_MYCTU Reviewed; 222 AA.
AC P9WG75; L0T3H3; P66916; P96260;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Thiamine-phosphate synthase;
DE Short=TP synthase;
DE Short=TPS;
DE EC=2.5.1.3 {ECO:0000269|PubMed:21818324};
DE AltName: Full=Thiamine-phosphate pyrophosphorylase;
DE Short=TMP pyrophosphorylase;
DE Short=TMP-PPase;
GN Name=thiE; OrderedLocusNames=Rv0414c; ORFNames=MTCY22G10.11c;
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 DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14569030; DOI=10.1073/pnas.2134250100;
RA Sassetti C.M., Rubin E.J.;
RT "Genetic requirements for mycobacterial survival during infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12989-12994(2003).
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, CATALYTIC ACTIVITY, KINETIC PARAMETERS, ACTIVITY REGULATION,
RP IDENTIFICATION OF INHIBITORS, AND IDENTIFICATION AS A DRUG TARGET.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21818324; DOI=10.1371/journal.pone.0022441;
RA Khare G., Kar R., Tyagi A.K.;
RT "Identification of inhibitors against Mycobacterium tuberculosis thiamin
RT phosphate synthase, an important target for the development of anti-TB
RT drugs.";
RL PLoS ONE 6:E22441-E22441(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) IN COMPLEX WITH PHOSPHATE.
RC STRAIN=ATCC 25618 / H37Rv;
RA McCulloch K.M., Ramamoorthy D., Ishida K., Guida W.C., Begley T.P.,
RA Ealick S.E.;
RT "Crystal structure and identification of potential inhibitor compounds for
RT Mycobacterium tuberculosis thiamin phosphate synthase.";
RL Submitted (JUL-2011) to the PDB data bank.
CC -!- FUNCTION: Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole
CC monophosphate (THZ-P) and 2-methyl-4-amino-5-hydroxymethyl pyrimidine
CC pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP).
CC {ECO:0000269|PubMed:21818324}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl
CC phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2
CC H(+) = CO2 + diphosphate + thiamine phosphate; Xref=Rhea:RHEA:47844,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37575, ChEBI:CHEBI:57841, ChEBI:CHEBI:62899; EC=2.5.1.3;
CC Evidence={ECO:0000269|PubMed:21818324};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate + 4-amino-2-
CC methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) = CO2 + diphosphate
CC + thiamine phosphate; Xref=Rhea:RHEA:47848, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33019, ChEBI:CHEBI:37575,
CC ChEBI:CHEBI:57841, ChEBI:CHEBI:62890; EC=2.5.1.3;
CC Evidence={ECO:0000269|PubMed:21818324};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 4-methyl-
CC 5-(2-phosphooxyethyl)-thiazole + H(+) = diphosphate + thiamine
CC phosphate; Xref=Rhea:RHEA:22328, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37575, ChEBI:CHEBI:57841,
CC ChEBI:CHEBI:58296; EC=2.5.1.3;
CC Evidence={ECO:0000269|PubMed:21818324};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: TPS activity is potently inhibited by several
CC molecules such as 4-{[(2-hydroxy-5-nitrophenyl)methylidene]amino}-5-
CC methyl-2-(propan-2-yl)phenol (NSC compound 33472) and 2-{5-[2,4,6-
CC (trinitrophenyl)amino]-1H-tetrazol-1-yl}ethanol (NSC compound 116720).
CC {ECO:0000269|PubMed:21818324}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5 uM for HMP-PP {ECO:0000269|PubMed:21818324};
CC KM=14 uM for THZ-P {ECO:0000269|PubMed:21818324};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis;
CC thiamine phosphate from 4-amino-2-methyl-5-diphosphomethylpyrimidine
CC and 4-methyl-5-(2-phosphoethyl)-thiazole: step 1/1.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene are shown to be
CC attenuated in a mouse tuberculosis model.
CC {ECO:0000269|PubMed:14569030}.
CC -!- SIMILARITY: Belongs to the thiamine-phosphate synthase family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43145.1; -; Genomic_DNA.
DR PIR; D70629; D70629.
DR RefSeq; NP_214928.1; NC_000962.3.
DR RefSeq; WP_003402115.1; NZ_NVQJ01000002.1.
DR PDB; 3O63; X-ray; 2.35 A; A/B=1-222.
DR PDBsum; 3O63; -.
DR AlphaFoldDB; P9WG75; -.
DR SMR; P9WG75; -.
DR STRING; 83332.Rv0414c; -.
DR PaxDb; P9WG75; -.
DR DNASU; 886391; -.
DR GeneID; 886391; -.
DR KEGG; mtu:Rv0414c; -.
DR TubercuList; Rv0414c; -.
DR eggNOG; COG0352; Bacteria.
DR OMA; ITAFQFR; -.
DR PhylomeDB; P9WG75; -.
DR UniPathway; UPA00060; UER00141.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004789; F:thiamine-phosphate diphosphorylase activity; IBA:GO_Central.
DR GO; GO:0009228; P:thiamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00564; TMP_TenI; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00097; TMP_synthase; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR036206; ThiamineP_synth_sf.
DR InterPro; IPR022998; ThiamineP_synth_TenI.
DR InterPro; IPR034291; TMP_synthase.
DR Pfam; PF02581; TMP-TENI; 1.
DR SUPFAM; SSF51391; SSF51391; 1.
DR TIGRFAMs; TIGR00693; thiE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Magnesium; Metal-binding; Reference proteome;
KW Thiamine biosynthesis; Transferase.
FT CHAIN 1..222
FT /note="Thiamine-phosphate synthase"
FT /id="PRO_0000157026"
FT BINDING 40..44
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 81
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 82
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 120
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 146..148
FT /ligand="2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-
FT ylidene]ethyl phosphate"
FT /ligand_id="ChEBI:CHEBI:62899"
FT /evidence="ECO:0000250"
FT BINDING 149
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-
FT ylidene]ethyl phosphate"
FT /ligand_id="ChEBI:CHEBI:62899"
FT /evidence="ECO:0000250"
FT HELIX 1..8
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:3O63"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 24..33
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 47..52
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 57..73
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 84..90
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 124..132
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 157..164
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:3O63"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 184..189
FT /evidence="ECO:0007829|PDB:3O63"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:3O63"
FT HELIX 207..219
FT /evidence="ECO:0007829|PDB:3O63"
SQ SEQUENCE 222 AA; 23271 MW; 2A9A32898F666C21 CRC64;
MHESRLASAR LYLCTDARRE RGDLAQFAEA ALAGGVDIIQ LRDKGSPGEL RFGPLQARDE
LAACEILADA AHRYGALFAV NDRADIARAA GADVLHLGQR DLPVNVARQI LAPDTLIGRS
THDPDQVAAA AAGDADYFCV GPCWPTPTKP GRAAPGLGLV RVAAELGGDD KPWFAIGGIN
AQRLPAVLDA GARRIVVVRA ITSADDPRAA AEQLRSALTA AN
