TYSY_STAAM
ID TYSY_STAAM Reviewed; 318 AA.
AC P67046; Q99U61;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
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=SAV1427;
OS Staphylococcus aureus (strain Mu50 / ATCC 700699).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=158878;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Mu50 / ATCC 700699;
RX PubMed=11418146; DOI=10.1016/s0140-6736(00)04403-2;
RA Kuroda M., Ohta T., Uchiyama I., Baba T., Yuzawa H., Kobayashi I., Cui L.,
RA Oguchi A., Aoki K., Nagai Y., Lian J.-Q., Ito T., Kanamori M.,
RA Matsumaru H., Maruyama A., Murakami H., Hosoyama A., Mizutani-Ui Y.,
RA Takahashi N.K., Sawano T., Inoue R., Kaito C., Sekimizu K., Hirakawa H.,
RA Kuhara S., Goto S., Yabuzaki J., Kanehisa M., Yamashita A., Oshima K.,
RA Furuya K., Yoshino C., Shiba T., Hattori M., Ogasawara N., Hayashi H.,
RA Hiramatsu K.;
RT "Whole genome sequencing of meticillin-resistant Staphylococcus aureus.";
RL Lancet 357:1225-1240(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 -!- SIMILARITY: Belongs to the thymidylate synthase family. Bacterial-type
CC ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}.
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DR EMBL; BA000017; BAB57589.1; -; Genomic_DNA.
DR RefSeq; WP_000934894.1; NC_002758.2.
DR PDB; 4DQ1; X-ray; 2.71 A; A/B=1-318.
DR PDBsum; 4DQ1; -.
DR AlphaFoldDB; P67046; -.
DR SMR; P67046; -.
DR World-2DPAGE; 0002:P67046; -.
DR PaxDb; P67046; -.
DR EnsemblBacteria; BAB57589; BAB57589; SAV1427.
DR KEGG; sav:SAV1427; -.
DR HOGENOM; CLU_021669_0_2_9; -.
DR OMA; KQYLDLC; -.
DR PhylomeDB; P67046; -.
DR BioCyc; SAUR158878:SAV_RS07690-MON; -.
DR UniPathway; UPA00575; -.
DR Proteomes; UP000002481; 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 Transferase.
FT CHAIN 1..318
FT /note="Thymidylate synthase"
FT /id="PRO_0000141018"
FT ACT_SITE 201
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT BINDING 26
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 181..182
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 221..224
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 224
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 232
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 262..264
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 317
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 4..19
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 31..42
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 57..69
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 74..78
FT /evidence="ECO:0007829|PDB:4DQ1"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 86..93
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 109..113
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 117..134
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 149..154
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 166..176
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:4DQ1"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 213..224
FT /evidence="ECO:0007829|PDB:4DQ1"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 228..246
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 250..264
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 268..276
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 284..287
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:4DQ1"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:4DQ1"
FT STRAND 301..305
FT /evidence="ECO:0007829|PDB:4DQ1"
SQ SEQUENCE 318 AA; 36825 MW; E7F41BA915C25D37 CRC64;
MLNSFDAAYH SLCEEVLEIG NTRNDRTNTG TISKFGHQLR FDLSKGFPLL TTKKVSFKLV
ATELLWFIKG DTNIQYLLKY NNNIWNEWAF ENYIKSDEYN GPDMTDFGHR ALSDPEFNEQ
YKEQMKQFKQ RILEDDTFAK QFGDLGNVYG KQWRDWVDKD GNHFDQLKTV IEQIKHNPDS
RRHIVSAWNP TEIDTMALPP CHTMFQFYVQ DGKLSCQLYQ RSADIFLGVP FNIASYALLT
HLIAKECGLE VGEFVHTFGD AHIYSNHIDA IQTQLARESF NPPTLKINSD KSIFDINYED
LEIVDYESHP AIKAPIAV
