TYSY_ECOLI
ID TYSY_ECOLI Reviewed; 264 AA.
AC P0A884; P00470; Q2MA10;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000303|PubMed:2223754, ECO:0000303|PubMed:3286637, ECO:0000303|PubMed:6308660};
DE Short=TS {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000303|PubMed:2223754, ECO:0000303|PubMed:3286637, ECO:0000303|PubMed:7708505};
DE Short=TSase {ECO:0000255|HAMAP-Rule:MF_00008};
DE EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637, ECO:0000269|PubMed:9826509};
GN Name=thyA {ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000303|PubMed:6308660};
GN OrderedLocusNames=b2827, JW2795;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=K12 / JM103 / ATCC 39403 / DSM 2829 / KCTC 1112 / NCIMB 12044;
RX PubMed=6308660; DOI=10.1073/pnas.80.16.4914;
RA Belfort M., Maley G.F., Pedersen-Lane J., Maley F.;
RT "Primary structure of the Escherichia coli thyA gene and its thymidylate
RT synthase product.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:4914-4918(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 63-264.
RX PubMed=3520484; DOI=10.1093/nar/14.11.4437;
RA Finch P.W., Wilson R.E., Brown K., Hickson I.D., Tomkinson A.E.,
RA Emmerson P.T.;
RT "Complete nucleotide sequence of the Escherichia coli recC gene and of the
RT thyA-recC intergenic region.";
RL Nucleic Acids Res. 14:4437-4451(1986).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF CYS-50.
RX PubMed=3286637; DOI=10.1016/s0021-9258(18)68543-6;
RA Maley G.F., Maley F.;
RT "Properties of a defined mutant of Escherichia coli thymidylate synthase.";
RL J. Biol. Chem. 263:7620-7627(1988).
RN [6]
RP MUTAGENESIS.
RX PubMed=1518803; DOI=10.1002/prot.340130407;
RA Kim C.W., Michaels M.L., Miller J.F.;
RT "Amino acid substitution analysis of E. coli thymidylate synthase: the
RT study of a highly conserved region at the N-terminus.";
RL Proteins 13:352-363(1992).
RN [7]
RP FUNCTION, AND MECHANISM OF TRANSLATION REGULATION.
RX PubMed=7708505; DOI=10.1093/nar/23.5.869;
RA Voeller D.M., Changchien L.-M., Maley G.F., Maley F., Takechi T.,
RA Turner R.E., Montfort W.R., Allegra C.J., Chu E.;
RT "Characterization of a specific interaction between Escherichia coli
RT thymidylate synthase and Escherichia coli thymidylate synthase mRNA.";
RL Nucleic Acids Res. 23:869-875(1995).
RN [8]
RP IDENTIFICATION BY 2D-GEL.
RX PubMed=9298644; DOI=10.1002/elps.1150180805;
RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.;
RT "Escherichia coli proteome analysis using the gene-protein database.";
RL Electrophoresis 18:1243-1251(1997).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) IN COMPLEX WITH DUMP, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVE SITE, AND SUBUNIT.
RX PubMed=2223754; DOI=10.1021/bi00482a004;
RA Montfort W.R., Perry K.M., Fauman E.B., Finer-Moore J.S., Maley G.F.,
RA Hardy L., Maley F., Stroud R.M.;
RT "Structure, multiple site binding, and segmental accommodation in
RT thymidylate synthase on binding dUMP and an anti-folate.";
RL Biochemistry 29:6964-6977(1990).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=2128651; DOI=10.1002/prot.340080406;
RA Perry K.M., Fauman E.B., Finer-Moore J.S., Montfort W.R., Maley G.F.,
RA Maley F., Stroud R.M.;
RT "Plastic adaptation toward mutations in proteins: structural comparison of
RT thymidylate synthases.";
RL Proteins 8:315-333(1990).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) IN COMPLEX WITH DIHYDROFOLATE AND
RP TMP.
RX PubMed=8312270; DOI=10.1021/bi00172a029;
RA Fauman E.B., Rutenber E.E., Maley G.F., Maley F., Stroud R.M.;
RT "Water-mediated substrate/product discrimination: the product complex of
RT thymidylate synthase at 1.83 A.";
RL Biochemistry 33:1502-1511(1994).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANT GLN-58 IN COMPLEX WITH
RP DUMP, ACTIVE SITE, AND SUBUNIT.
RX PubMed=8973201; DOI=10.1021/bi961269r;
RA Sage C.R., Rutenber E.E., Stout T.J., Stroud R.M.;
RT "An essential role for water in an enzyme reaction mechanism: the crystal
RT structure of the thymidylate synthase mutant E58Q.";
RL Biochemistry 35:16270-16281(1996).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANT GLU-126 IN COMPLEX WITH
RP DUMP, MUTAGENESIS OF ARG-126, REACTION MECHANISM, AND ACTIVE SITE.
RX PubMed=9416600; DOI=10.1002/pro.5560061203;
RA Strop P., Changchien L., Maley F., Montfort W.R.;
RT "Crystal structures of a marginally active thymidylate synthase mutant, Arg
RT 126-->Glu.";
RL Protein Sci. 6:2504-2511(1997).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ALA-177 IN COMPLEX WITH
RP DUMP, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF ASN-177.
RX PubMed=9826509; DOI=10.1006/jmbi.1998.2205;
RA Reyes C.L., Sage C.R., Rutenber E.E., Nissen R.M., Finer-Moore J.S.,
RA Stroud R.M.;
RT "Inactivity of N229A thymidylate synthase due to water-mediated effects:
RT isolating a late stage in methyl transfer.";
RL J. Mol. Biol. 284:699-712(1998).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS).
RX PubMed=10944209; DOI=10.1073/pnas.97.17.9367;
RA Erlanson D.A., Braisted A.C., Raphael D.R., Randal M., Stroud R.M.,
RA Gordon E.M., Wells J.A.;
RT "Site-directed ligand discovery.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9367-9372(2000).
CC -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine-5'-
CC monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while
CC utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and
CC reductant in the reaction, yielding dihydrofolate (DHF) as a by-product
CC (PubMed:3286637, PubMed:2223754, PubMed:9826509). This enzymatic
CC reaction provides an intracellular de novo source of dTMP, an essential
CC precursor for DNA biosynthesis. This protein also binds to its mRNA
CC thus repressing its own translation (PubMed:7708505).
CC {ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637,
CC ECO:0000269|PubMed:7708505, ECO:0000269|PubMed:9826509}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-
CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC EC=2.1.1.45; Evidence={ECO:0000255|HAMAP-Rule:MF_00008,
CC ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637,
CC ECO:0000269|PubMed:9826509};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for dUMP {ECO:0000269|PubMed:3286637};
CC KM=25 uM for 5,10-methylenetetrahydrofolate
CC {ECO:0000269|PubMed:3286637};
CC KM=4.1 uM for dUMP {ECO:0000269|PubMed:9826509};
CC KM=13.6 uM for 5,10-methylenetetrahydrofolate
CC {ECO:0000269|PubMed:9826509};
CC Vmax=5.47 umol/min/mg enzyme {ECO:0000269|PubMed:3286637};
CC Note=kcat is 8.8 sec(-1). {ECO:0000269|PubMed:9826509};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_00008}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:2223754,
CC ECO:0000269|PubMed:8973201}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00008}.
CC -!- PTM: Although not discussed in the published references, Met-1 is
CC represented in the submitted PDB entries as being modified by either a
CC formyl, or a carboxyl group. The N-terminal is probably N-
CC (dihydroxymethyl)methionine, the hydrated form of N-formylmethionine.
CC -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type
CC ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}.
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DR EMBL; J01710; AAA24675.1; -; Genomic_DNA.
DR EMBL; U29581; AAB40474.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75866.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76896.1; -; Genomic_DNA.
DR EMBL; X03966; CAA27600.1; -; Genomic_DNA.
DR PIR; A00549; SYECT.
DR RefSeq; NP_417304.1; NC_000913.3.
DR RefSeq; WP_000816232.1; NZ_STEB01000034.1.
DR PDB; 1AIQ; X-ray; 2.20 A; A/B=1-264.
DR PDB; 1AJM; X-ray; 2.40 A; A=1-264.
DR PDB; 1AN5; X-ray; 2.60 A; A/B=1-264.
DR PDB; 1AOB; X-ray; 2.10 A; A=1-264.
DR PDB; 1AXW; X-ray; 1.70 A; A/B=1-264.
DR PDB; 1BDU; X-ray; 2.10 A; A=1-264.
DR PDB; 1BID; X-ray; 2.20 A; A=1-264.
DR PDB; 1BJG; X-ray; 2.30 A; A=1-264.
DR PDB; 1BQ1; X-ray; 2.50 A; A/B=1-264.
DR PDB; 1BQ2; X-ray; 2.20 A; A=1-264.
DR PDB; 1DDU; X-ray; 2.10 A; A/B=1-264.
DR PDB; 1DNA; X-ray; 2.20 A; A/B=1-264.
DR PDB; 1EV5; X-ray; 1.70 A; A=1-264.
DR PDB; 1EV8; X-ray; 2.60 A; A=1-264.
DR PDB; 1EVF; X-ray; 1.70 A; A=1-264.
DR PDB; 1EVG; X-ray; 2.00 A; A=1-264.
DR PDB; 1F4B; X-ray; 1.75 A; A=1-264.
DR PDB; 1F4C; X-ray; 2.00 A; A/B=1-264.
DR PDB; 1F4D; X-ray; 2.15 A; A/B=1-264.
DR PDB; 1F4E; X-ray; 1.90 A; A=1-264.
DR PDB; 1F4F; X-ray; 2.00 A; A/B=1-264.
DR PDB; 1F4G; X-ray; 1.75 A; A/B=1-264.
DR PDB; 1FFL; X-ray; 2.94 A; A=1-264.
DR PDB; 1FWM; X-ray; 2.20 A; A/B=1-264.
DR PDB; 1JG0; X-ray; 2.00 A; A/B=1-264.
DR PDB; 1JTQ; X-ray; 2.50 A; A/B=1-264.
DR PDB; 1JTU; X-ray; 2.20 A; A/B=1-264.
DR PDB; 1JUT; X-ray; 2.70 A; A/B=1-264.
DR PDB; 1KCE; X-ray; 2.00 A; A/B=1-264.
DR PDB; 1KZI; X-ray; 1.75 A; A/B=1-264.
DR PDB; 1KZJ; X-ray; 2.60 A; A/B/C/D/E/F=1-264.
DR PDB; 1NCE; X-ray; 2.40 A; A/B=1-264.
DR PDB; 1QQQ; X-ray; 1.50 A; A=1-264.
DR PDB; 1SYN; X-ray; 2.00 A; A/B=1-264.
DR PDB; 1TDU; X-ray; 2.10 A; A/B=1-264.
DR PDB; 1TJS; X-ray; 2.20 A; A=1-264.
DR PDB; 1TLC; X-ray; 2.10 A; A/B=1-264.
DR PDB; 1TLS; X-ray; 2.60 A; A/B=1-264.
DR PDB; 1TRG; X-ray; 1.90 A; A=1-264.
DR PDB; 1TSD; X-ray; 1.95 A; A/B=1-264.
DR PDB; 1TSN; X-ray; 2.20 A; A=1-264.
DR PDB; 1TYS; X-ray; 1.80 A; A=1-264.
DR PDB; 1ZPR; X-ray; 2.50 A; A/B=1-264.
DR PDB; 2A9W; X-ray; 1.65 A; A/B/C/D=1-264.
DR PDB; 2BBQ; X-ray; 2.30 A; A/B=1-264.
DR PDB; 2FTN; X-ray; 1.60 A; A=1-264.
DR PDB; 2FTO; X-ray; 2.00 A; X=1-264.
DR PDB; 2FTQ; X-ray; 1.81 A; A=1-264.
DR PDB; 2G8X; X-ray; 1.83 A; A/B=1-264.
DR PDB; 2KCE; X-ray; 2.20 A; A/B=1-264.
DR PDB; 2TSC; X-ray; 1.97 A; A/B=1-264.
DR PDB; 2VET; X-ray; 2.20 A; A=1-264.
DR PDB; 2VF0; X-ray; 3.00 A; A/B=1-264.
DR PDB; 3B5B; X-ray; 2.70 A; A/B=1-264.
DR PDB; 3B9H; X-ray; 2.49 A; A=1-264.
DR PDB; 3BFI; X-ray; 2.20 A; A=1-264.
DR PDB; 3BGX; X-ray; 1.93 A; A=1-264.
DR PDB; 3BHL; X-ray; 1.40 A; A/B=1-264.
DR PDB; 3BHR; X-ray; 1.90 A; A=1-264.
DR PDB; 3TMS; X-ray; 2.10 A; A=1-264.
DR PDB; 4F2V; X-ray; 2.49 A; A/B=1-264.
DR PDB; 4GEV; X-ray; 1.30 A; A/B=1-264.
DR PDB; 4ISK; X-ray; 1.75 A; A/B/C/D/E/F/G/H=2-264.
DR PDB; 6CDZ; X-ray; 2.40 A; A/B=1-263.
DR PDB; 6NNR; X-ray; 1.05 A; A/B=1-264.
DR PDB; 7JX1; X-ray; 1.82 A; A/B=1-264.
DR PDB; 7JXF; X-ray; 1.50 A; A/B=1-264.
DR PDBsum; 1AIQ; -.
DR PDBsum; 1AJM; -.
DR PDBsum; 1AN5; -.
DR PDBsum; 1AOB; -.
DR PDBsum; 1AXW; -.
DR PDBsum; 1BDU; -.
DR PDBsum; 1BID; -.
DR PDBsum; 1BJG; -.
DR PDBsum; 1BQ1; -.
DR PDBsum; 1BQ2; -.
DR PDBsum; 1DDU; -.
DR PDBsum; 1DNA; -.
DR PDBsum; 1EV5; -.
DR PDBsum; 1EV8; -.
DR PDBsum; 1EVF; -.
DR PDBsum; 1EVG; -.
DR PDBsum; 1F4B; -.
DR PDBsum; 1F4C; -.
DR PDBsum; 1F4D; -.
DR PDBsum; 1F4E; -.
DR PDBsum; 1F4F; -.
DR PDBsum; 1F4G; -.
DR PDBsum; 1FFL; -.
DR PDBsum; 1FWM; -.
DR PDBsum; 1JG0; -.
DR PDBsum; 1JTQ; -.
DR PDBsum; 1JTU; -.
DR PDBsum; 1JUT; -.
DR PDBsum; 1KCE; -.
DR PDBsum; 1KZI; -.
DR PDBsum; 1KZJ; -.
DR PDBsum; 1NCE; -.
DR PDBsum; 1QQQ; -.
DR PDBsum; 1SYN; -.
DR PDBsum; 1TDU; -.
DR PDBsum; 1TJS; -.
DR PDBsum; 1TLC; -.
DR PDBsum; 1TLS; -.
DR PDBsum; 1TRG; -.
DR PDBsum; 1TSD; -.
DR PDBsum; 1TSN; -.
DR PDBsum; 1TYS; -.
DR PDBsum; 1ZPR; -.
DR PDBsum; 2A9W; -.
DR PDBsum; 2BBQ; -.
DR PDBsum; 2FTN; -.
DR PDBsum; 2FTO; -.
DR PDBsum; 2FTQ; -.
DR PDBsum; 2G8X; -.
DR PDBsum; 2KCE; -.
DR PDBsum; 2TSC; -.
DR PDBsum; 2VET; -.
DR PDBsum; 2VF0; -.
DR PDBsum; 3B5B; -.
DR PDBsum; 3B9H; -.
DR PDBsum; 3BFI; -.
DR PDBsum; 3BGX; -.
DR PDBsum; 3BHL; -.
DR PDBsum; 3BHR; -.
DR PDBsum; 3TMS; -.
DR PDBsum; 4F2V; -.
DR PDBsum; 4GEV; -.
DR PDBsum; 4ISK; -.
DR PDBsum; 6CDZ; -.
DR PDBsum; 6NNR; -.
DR PDBsum; 7JX1; -.
DR PDBsum; 7JXF; -.
DR AlphaFoldDB; P0A884; -.
DR SMR; P0A884; -.
DR BioGRID; 4262058; 217.
DR DIP; DIP-48261N; -.
DR IntAct; P0A884; 5.
DR STRING; 511145.b2827; -.
DR BindingDB; P0A884; -.
DR ChEMBL; CHEMBL2555; -.
DR DrugBank; DB02031; (6S)-5,6,7,8-tetrahydrofolic acid.
DR DrugBank; DB04447; 1,4-Dithiothreitol.
DR DrugBank; DB03541; 10-Propargyl-5,8-Dideazafolic Acid.
DR DrugBank; DB03274; 2',5'-Dideoxyuridine.
DR DrugBank; DB04457; 2'-Deoxyguanosine-5'-Monophosphate.
DR DrugBank; DB02256; 2'-Deoxyuridine.
DR DrugBank; DB08131; 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-3-METHYL-BUTYRIC ACID.
DR DrugBank; DB04696; 4-CHLORO-3',3''-DIBROMOPHENOL-1,8-NAPHTHALEIN.
DR DrugBank; DB02301; 5,10-Methylene-6-Hydrofolic Acid.
DR DrugBank; DB03761; 5-fluoro-2'-deoxyuridine-5'-monophosphate.
DR DrugBank; DB03800; Deoxyuridine monophosphate.
DR DrugBank; DB02467; L-methionine (S)-S-oxide.
DR DrugBank; DB02223; LY231514 tetra glu.
DR DrugBank; DB03038; LY341770.
DR DrugBank; DB03157; N,O-didansyl-L-tyrosine.
DR DrugBank; DB03818; N-[Tosyl-D-Prolinyl]Amino-Ethanethiol.
DR DrugBank; DB02899; N-Carboxymethionine.
DR DrugBank; DB04586; o-Bromophenol.
DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine.
DR DrugBank; DB04503; Sp-722.
DR DrugBank; DB03558; SP-876.
DR DrugBank; DB02752; Tosyl-D-Proline.
DR DrugCentral; P0A884; -.
DR jPOST; P0A884; -.
DR PaxDb; P0A884; -.
DR PRIDE; P0A884; -.
DR EnsemblBacteria; AAC75866; AAC75866; b2827.
DR EnsemblBacteria; BAE76896; BAE76896; BAE76896.
DR GeneID; 66673306; -.
DR GeneID; 949035; -.
DR KEGG; ecj:JW2795; -.
DR KEGG; eco:b2827; -.
DR PATRIC; fig|1411691.4.peg.3908; -.
DR EchoBASE; EB0995; -.
DR eggNOG; COG0207; Bacteria.
DR HOGENOM; CLU_021669_0_0_6; -.
DR InParanoid; P0A884; -.
DR OMA; KQYLDLC; -.
DR PhylomeDB; P0A884; -.
DR BioCyc; EcoCyc:THYMIDYLATESYN-MON; -.
DR BioCyc; MetaCyc:THYMIDYLATESYN-MON; -.
DR BRENDA; 2.1.1.45; 2026.
DR SABIO-RK; P0A884; -.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; P0A884; -.
DR PRO; PR:P0A884; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004799; F:thymidylate synthase activity; IDA:EcoCyc.
DR GO; GO:0006231; P:dTMP biosynthetic process; IDA:EcoCyc.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0009314; P:response to radiation; IMP:EcoCyc.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.30.572.10; -; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR InterPro; IPR000398; Thymidylate_synthase.
DR InterPro; IPR020940; Thymidylate_synthase_AS.
DR PANTHER; PTHR11548; PTHR11548; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 2.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Formylation;
KW Methyltransferase; Nucleotide biosynthesis; Reference proteome; Repressor;
KW RNA-binding; Transferase; Translation regulation.
FT CHAIN 1..264
FT /note="Thymidylate synthase"
FT /id="PRO_0000140954"
FT ACT_SITE 146
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008,
FT ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:8973201,
FT ECO:0000269|PubMed:9416600"
FT BINDING 21
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:2223754,
FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE,
FT ECO:0007744|PDB:2TSC"
FT BINDING 51
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000305|PubMed:8312270,
FT ECO:0007744|PDB:1TYS"
FT BINDING 126..127
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:2223754,
FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE,
FT ECO:0007744|PDB:2TSC"
FT BINDING 166..169
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:2223754,
FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE,
FT ECO:0007744|PDB:2TSC"
FT BINDING 169
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000305|PubMed:8312270,
FT ECO:0007744|PDB:1TYS"
FT BINDING 177
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:2223754,
FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE,
FT ECO:0007744|PDB:2TSC"
FT BINDING 207..209
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:2223754,
FT ECO:0000269|PubMed:8973201, ECO:0007744|PDB:1KCE,
FT ECO:0007744|PDB:2TSC"
FT BINDING 263
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000305|PubMed:8312270,
FT ECO:0007744|PDB:1TYS"
FT MUTAGEN 50
FT /note="C->Y: Shows 0.2% of wild-type catalytic activity,
FT but substrate affinity is not affected."
FT /evidence="ECO:0000269|PubMed:3286637"
FT MUTAGEN 126
FT /note="R->E: Shows 2000-fold decrease in catalytic activity
FT and 600-fold decrease in affinity for dUMP."
FT /evidence="ECO:0000269|PubMed:9416600"
FT MUTAGEN 177
FT /note="N->A: Shows 200-fold decrease in catalytic activity,
FT 20-fold decrease in affinity for dUMP, and 10-fold decrease
FT in affinity for mTHF."
FT /evidence="ECO:0000269|PubMed:9826509"
FT HELIX 2..14
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:2G8X"
FT STRAND 26..37
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:2A9W"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1JG0"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:1JG0"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1JG0"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 135..140
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 146..155
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 158..169
FT /evidence="ECO:0007829|PDB:6NNR"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 173..192
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 195..209
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 213..220
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:6NNR"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:1AXW"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:6NNR"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:6NNR"
SQ SEQUENCE 264 AA; 30480 MW; 0E6D88ED98D24D22 CRC64;
MKQYLELMQK VLDEGTQKND RTGTGTLSIF GHQMRFNLQD GFPLVTTKRC HLRSIIHELL
WFLQGDTNIA YLHENNVTIW DEWADENGDL GPVYGKQWRA WPTPDGRHID QITTVLNQLK
NDPDSRRIIV SAWNVGELDK MALAPCHAFF QFYVADGKLS CQLYQRSCDV FLGLPFNIAS
YALLVHMMAQ QCDLEVGDFV WTGGDTHLYS NHMDQTHLQL SREPRPLPKL IIKRKPESIF
DYRFEDFEIE GYDPHPGIKA PVAI
