TYSY_ENTFA
ID TYSY_ENTFA Reviewed; 315 AA.
AC Q834R3;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 117.
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}; OrderedLocusNames=EF_1576;
OS Enterococcus faecalis (strain ATCC 700802 / V583).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=226185;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700802 / V583;
RX PubMed=12663927; DOI=10.1126/science.1080613;
RA Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R.,
RA Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,
RA Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C.,
RA DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C.,
RA Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M.,
RA Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.;
RT "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus
RT faecalis.";
RL Science 299:2071-2074(2003).
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 -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type
CC ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}.
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DR EMBL; AE016830; AAO81363.1; -; Genomic_DNA.
DR RefSeq; NP_815293.1; NC_004668.1.
DR RefSeq; WP_002357569.1; NZ_KE136528.1.
DR PDB; 3UWL; X-ray; 2.07 A; A/B/C/D=1-315.
DR PDB; 4O7U; X-ray; 2.40 A; A/B/C/D=1-315.
DR PDB; 5J7W; X-ray; 2.50 A; A/B/C/D=1-315.
DR PDB; 6QXS; X-ray; 2.88 A; A/B/C/D=1-315.
DR PDB; 6QYA; X-ray; 1.76 A; A/B/C/D=1-315.
DR PDBsum; 3UWL; -.
DR PDBsum; 4O7U; -.
DR PDBsum; 5J7W; -.
DR PDBsum; 6QXS; -.
DR PDBsum; 6QYA; -.
DR AlphaFoldDB; Q834R3; -.
DR SMR; Q834R3; -.
DR STRING; 226185.EF_1576; -.
DR BindingDB; Q834R3; -.
DR ChEMBL; CHEMBL1795144; -.
DR DrugCentral; Q834R3; -.
DR EnsemblBacteria; AAO81363; AAO81363; EF_1576.
DR GeneID; 60893881; -.
DR KEGG; efa:EF1576; -.
DR PATRIC; fig|226185.45.peg.1929; -.
DR eggNOG; COG0207; Bacteria.
DR HOGENOM; CLU_021669_0_2_9; -.
DR OMA; KQYLDLC; -.
DR BRENDA; 2.1.1.45; 2095.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000001415; 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; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Methyltransferase; Nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..315
FT /note="Thymidylate synthase"
FT /id="PRO_0000140957"
FT ACT_SITE 197
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT BINDING 22
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 177..178
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 217..220
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 220
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 228
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 258..260
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 314
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..15
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 27..38
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 71..75
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:3UWL"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 111..115
FT /evidence="ECO:0007829|PDB:4O7U"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 162..172
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:6QYA"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 209..220
FT /evidence="ECO:0007829|PDB:6QYA"
FT TURN 221..224
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 225..242
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 246..260
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 264..271
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:6QYA"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:6QYA"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:6QYA"
SQ SEQUENCE 315 AA; 36344 MW; 0593A11D77D2D0A2 CRC64;
MEEAYLALGK KILEEGHFKE DRTGTGTYSL FGYQMRFDLA KGFPLLTTKR VPFGLIKSEL
LWFLKGDTNI RYLLERNNHI WDEWAFERYV KSADYQGPDM TDFGHRVLQD PAFAEQYKEE
HQKFCDAILN DAEFAEKYGE LGNIYGAQWR HWETKDGSFI DQLANVIEMI KTNPDSRRLI
VSAWNPEDVP SMALPPCHTM FQFYVNEGKL SCQLYQRSAD VFLGVPFNIA SYALLTHLIA
HETGLEVGEF VHTLGDAHLY QNHVEQMQEQ LSREVRSFPT LVLNPDKASV FDFDMEDIKV
EGYDPHPTIK APIAV
