THRC_MYCTU
ID THRC_MYCTU Reviewed; 360 AA.
AC P9WG59; L0T6F8; P66902; Q10610;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Threonine synthase;
DE Short=TS;
DE EC=4.2.3.1;
GN Name=thrC; OrderedLocusNames=Rv1295; ORFNames=MTCY373.15;
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 PUPYLATION AT LYS-151, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20066036; DOI=10.1371/journal.pone.0008589;
RA Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E.,
RA Gygi S.P., Darwin K.H.;
RT "Prokaryotic ubiquitin-like protein (Pup) proteome of Mycobacterium
RT tuberculosis.";
RL PLoS ONE 5:E8589-E8589(2010).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PLP, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, SUBUNIT, AND REACTION MECHANISM.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18621388; DOI=10.1016/j.jmb.2008.05.086;
RA Covarrubias A.S., Hogbom M., Bergfors T., Carroll P., Mannerstedt K.,
RA Oscarson S., Parish T., Jones T.A., Mowbray S.L.;
RT "Structural, biochemical, and in vivo investigations of the threonine
RT synthase from Mycobacterium tuberculosis.";
RL J. Mol. Biol. 381:622-633(2008).
CC -!- FUNCTION: Catalyzes the gamma-elimination of phosphate from L-
CC phosphohomoserine and the beta-addition of water to produce L-
CC threonine. {ECO:0000269|PubMed:18621388}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-homoserine = L-threonine + phosphate;
CC Xref=Rhea:RHEA:10840, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57590, ChEBI:CHEBI:57926; EC=4.2.3.1;
CC Evidence={ECO:0000269|PubMed:18621388};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:18621388};
CC -!- ACTIVITY REGULATION: Activity is not influenced by the addition of S-
CC adenosylmethionine, the allosteric activator of TS from Arabidopsis
CC thaliana. {ECO:0000269|PubMed:18621388}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 mM for O-phospho-L-homoserine (at pH 8.4 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:18621388};
CC pH dependence:
CC Optimum pH is 9.5-10.5. Is inactive at pH values of 7 or less.
CC {ECO:0000269|PubMed:18621388};
CC Temperature dependence:
CC Loses less than 10% of the initial activity during a 10 minutes
CC incubation at 65 degrees Celsius. At 80 degrees Celsius, 90% of the
CC activity is lost over the same time period.
CC {ECO:0000269|PubMed:18621388};
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC from L-aspartate: step 5/5.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18621388}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the threonine synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44052.1; -; Genomic_DNA.
DR PIR; C70773; C70773.
DR RefSeq; NP_215811.1; NC_000962.3.
DR RefSeq; WP_003406652.1; NZ_NVQJ01000030.1.
DR PDB; 2D1F; X-ray; 2.50 A; A/B=1-360.
DR PDBsum; 2D1F; -.
DR AlphaFoldDB; P9WG59; -.
DR SMR; P9WG59; -.
DR STRING; 83332.Rv1295; -.
DR iPTMnet; P9WG59; -.
DR PaxDb; P9WG59; -.
DR PRIDE; P9WG59; -.
DR DNASU; 886957; -.
DR GeneID; 45425269; -.
DR GeneID; 886957; -.
DR KEGG; mtu:Rv1295; -.
DR TubercuList; Rv1295; -.
DR eggNOG; COG0498; Bacteria.
DR OMA; MWGFQAS; -.
DR PhylomeDB; P9WG59; -.
DR BRENDA; 4.2.3.1; 3445.
DR UniPathway; UPA00050; UER00065.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:MTBBASE.
DR GO; GO:0004795; F:threonine synthase activity; IDA:MTBBASE.
DR GO; GO:0019344; P:cysteine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009088; P:threonine biosynthetic process; IMP:MTBBASE.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR000634; Ser/Thr_deHydtase_PyrdxlP-BS.
DR InterPro; IPR004450; Thr_synthase-like.
DR InterPro; IPR026260; Thr_Synthase_bac/arc.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00291; PALP; 1.
DR PIRSF; PIRSF038945; Thr_synthase; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
DR TIGRFAMs; TIGR00260; thrC; 1.
DR PROSITE; PS00165; DEHYDRATASE_SER_THR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Amino-acid biosynthesis; Isopeptide bond; Lyase;
KW Pyridoxal phosphate; Reference proteome; Threonine biosynthesis;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..360
FT /note="Threonine synthase"
FT /id="PRO_0000185637"
FT BINDING 95
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:18621388"
FT BINDING 196..200
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:18621388"
FT BINDING 326
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:18621388"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MOD_RES 69
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:18621388"
FT CROSSLNK 151
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-Cter in protein Pup)"
FT /evidence="ECO:0000269|PubMed:20066036"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 70..82
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 95..107
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 122..130
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 134..140
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 142..155
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 167..173
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 175..184
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 199..213
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 222..228
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 258..268
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 277..291
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 297..312
FT /evidence="ECO:0007829|PDB:2D1F"
FT STRAND 320..325
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 333..337
FT /evidence="ECO:0007829|PDB:2D1F"
FT HELIX 350..355
FT /evidence="ECO:0007829|PDB:2D1F"
SQ SEQUENCE 360 AA; 37322 MW; 43D27F553D5774B6 CRC64;
MTVPPTATHQ PWPGVIAAYR DRLPVGDDWT PVTLLEGGTP LIAATNLSKQ TGCTIHLKVE
GLNPTGSFKD RGMTMAVTDA LAHGQRAVLC ASTGNTSASA AAYAARAGIT CAVLIPQGKI
AMGKLAQAVM HGAKIIQIDG NFDDCLELAR KMAADFPTIS LVNSVNPVRI EGQKTAAFEI
VDVLGTAPDV HALPVGNAGN ITAYWKGYTE YHQLGLIDKL PRMLGTQAAG AAPLVLGEPV
SHPETIATAI RIGSPASWTS AVEAQQQSKG RFLAASDEEI LAAYHLVARV EGVFVEPASA
ASIAGLLKAI DDGWVARGST VVCTVTGNGL KDPDTALKDM PSVSPVPVDP VAVVEKLGLA
