TYSY_ECO57
ID TYSY_ECO57 Reviewed; 264 AA.
AC P0A886; P00470;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Thymidylate synthase {ECO:0000255|HAMAP-Rule:MF_00008};
DE Short=TS {ECO:0000255|HAMAP-Rule:MF_00008};
DE Short=TSase {ECO:0000255|HAMAP-Rule:MF_00008};
DE EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008};
GN Name=thyA {ECO:0000255|HAMAP-Rule:MF_00008};
GN OrderedLocusNames=Z4144, ECs3684;
OS Escherichia coli O157:H7.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83334;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=O157:H7 / EDL933 / ATCC 700927 / EHEC;
RX PubMed=11206551; DOI=10.1038/35054089;
RA Perna N.T., Plunkett G. III, Burland V., Mau B., Glasner J.D., Rose D.J.,
RA Mayhew G.F., Evans P.S., Gregor J., Kirkpatrick H.A., Posfai G.,
RA Hackett J., Klink S., Boutin A., Shao Y., Miller L., Grotbeck E.J.,
RA Davis N.W., Lim A., Dimalanta E.T., Potamousis K., Apodaca J.,
RA Anantharaman T.S., Lin J., Yen G., Schwartz D.C., Welch R.A.,
RA Blattner F.R.;
RT "Genome sequence of enterohaemorrhagic Escherichia coli O157:H7.";
RL Nature 409:529-533(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=O157:H7 / Sakai / RIMD 0509952 / EHEC;
RX PubMed=11258796; DOI=10.1093/dnares/8.1.11;
RA Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K.,
RA Han C.-G., Ohtsubo E., Nakayama K., Murata T., Tanaka M., Tobe T., Iida T.,
RA Takami H., Honda T., Sasakawa C., Ogasawara N., Yasunaga T., Kuhara S.,
RA Shiba T., Hattori M., Shinagawa H.;
RT "Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and
RT genomic comparison with a laboratory strain K-12.";
RL DNA Res. 8:11-22(2001).
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-
CC product. This enzymatic reaction provides an intracellular de novo
CC source of dTMP, an essential precursor for DNA biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_00008}.
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 -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_00008}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00008}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00008}.
CC -!- PTM: The N-terminal is probably N-(dihydroxymethyl)-methionine, the
CC hydrated form of N-formylmethionine. {ECO:0000250}.
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; AE005174; AAG57938.1; -; Genomic_DNA.
DR EMBL; BA000007; BAB37107.1; -; Genomic_DNA.
DR PIR; D91089; D91089.
DR PIR; F85934; F85934.
DR RefSeq; NP_311711.1; NC_002695.1.
DR RefSeq; WP_000816232.1; NZ_SWKA01000005.1.
DR PDB; 4LRR; X-ray; 2.41 A; A=1-264.
DR PDBsum; 4LRR; -.
DR AlphaFoldDB; P0A886; -.
DR SMR; P0A886; -.
DR STRING; 155864.EDL933_4006; -.
DR EnsemblBacteria; AAG57938; AAG57938; Z4144.
DR EnsemblBacteria; BAB37107; BAB37107; ECs_3684.
DR GeneID; 66673306; -.
DR GeneID; 916501; -.
DR KEGG; ece:Z4144; -.
DR KEGG; ecs:ECs_3684; -.
DR PATRIC; fig|386585.9.peg.3851; -.
DR eggNOG; COG0207; Bacteria.
DR HOGENOM; CLU_021669_0_0_6; -.
DR OMA; KQYLDLC; -.
DR SABIO-RK; P0A886; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000000558; Chromosome.
DR Proteomes; UP000002519; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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; Formylation; Methyltransferase;
KW Nucleotide biosynthesis; Reference proteome; Transferase.
FT CHAIN 1..264
FT /note="Thymidylate synthase"
FT /id="PRO_0000140955"
FT ACT_SITE 146
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
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:0000255|HAMAP-Rule:MF_00008"
FT BINDING 51
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT BINDING 126..127
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
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:0000255|HAMAP-Rule:MF_00008"
FT BINDING 169
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
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:0000255|HAMAP-Rule:MF_00008"
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:0000255|HAMAP-Rule:MF_00008"
FT BINDING 263
FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate"
FT /ligand_id="ChEBI:CHEBI:15636"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT HELIX 2..14
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 25..37
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:4LRR"
FT TURN 79..83
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 135..140
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 146..155
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 158..169
FT /evidence="ECO:0007829|PDB:4LRR"
FT TURN 170..173
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 174..191
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 195..209
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 213..220
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:4LRR"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:4LRR"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:4LRR"
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
