TYSY1_BACSU
ID TYSY1_BACSU Reviewed; 279 AA.
AC P0CI79; O30395; O30396; P42326;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Thymidylate synthase 1 {ECO:0000255|HAMAP-Rule:MF_00008};
DE Short=TS 1 {ECO:0000255|HAMAP-Rule:MF_00008};
DE Short=TSase 1 {ECO:0000255|HAMAP-Rule:MF_00008};
DE EC=2.1.1.45 {ECO:0000255|HAMAP-Rule:MF_00008};
DE AltName: Full=Thymidylate synthase A {ECO:0000303|PubMed:9648749};
DE Short=TS A {ECO:0000303|PubMed:9648749};
DE Short=TSase A {ECO:0000303|PubMed:9648749};
GN Name=thyA1 {ECO:0000255|HAMAP-Rule:MF_00008}; OrderedLocusNames=BSU17680;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RX PubMed=7704257; DOI=10.1099/13500872-141-2-291;
RA Tam N.H., Borriss R.;
RT "The thyA gene from Bacillus subtilis exhibits similarity with the phage
RT phi 3T thymidylate synthase gene.";
RL Microbiology 141:291-297(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 49-279.
RC STRAIN=ATCC 6633 / NCIMB 8054 / CCM1999;
RX PubMed=9648749; DOI=10.1007/pl00008625;
RA Tam N.H., Borriss R.;
RT "Genes encoding thymidylate synthases A and B in the genus Bacillus are
RT members of two distinct families.";
RL Mol. Gen. Genet. 258:427-430(1998).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=9778348; DOI=10.1021/bi981270l;
RA Stout T.J., Schellenberger U., Santi D.V., Stroud R.M.;
RT "Crystal structures of a unique thermal-stable thymidylate synthase from
RT Bacillus subtilis.";
RL Biochemistry 37:14736-14747(1998).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=10091656; DOI=10.1110/ps.8.3.538;
RA Fox K.M., Maley F., Garibian A., Changchien L.M., van Roey P.;
RT "Crystal structure of thymidylate synthase A from Bacillus subtilis.";
RL Protein Sci. 8:538-544(1999).
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable. Active at 46 degrees Celsius.;
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 -!- MISCELLANEOUS: B.subtilis strain 168 possesses two thymidylate
CC synthases, a major form ThyA and a minor form ThyB.
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; X78560; CAA55307.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB13652.1; -; Genomic_DNA.
DR EMBL; AF004102; AAC26324.1; -; Genomic_DNA.
DR PIR; I40494; I40494.
DR RefSeq; NP_389651.1; NC_000964.3.
DR RefSeq; WP_003244896.1; NZ_JNCM01000035.1.
DR PDB; 1B02; X-ray; 2.50 A; A=1-279.
DR PDB; 1BKO; X-ray; 2.75 A; A/B/C/D=2-279.
DR PDB; 1BKP; X-ray; 1.70 A; A/B=2-279.
DR PDB; 1BSF; X-ray; 2.20 A; A/B=2-279.
DR PDB; 1BSP; X-ray; 2.50 A; A/B=2-279.
DR PDBsum; 1B02; -.
DR PDBsum; 1BKO; -.
DR PDBsum; 1BKP; -.
DR PDBsum; 1BSF; -.
DR PDBsum; 1BSP; -.
DR AlphaFoldDB; P0CI79; -.
DR SMR; P0CI79; -.
DR STRING; 224308.BSU17680; -.
DR DrugBank; DB03761; 5-fluoro-2'-deoxyuridine-5'-monophosphate.
DR PaxDb; P0CI79; -.
DR PRIDE; P0CI79; -.
DR EnsemblBacteria; CAB13652; CAB13652; BSU_17680.
DR GeneID; 939555; -.
DR KEGG; bsu:BSU17680; -.
DR PATRIC; fig|224308.179.peg.1922; -.
DR eggNOG; COG0207; Bacteria.
DR InParanoid; P0CI79; -.
DR OMA; WNEWEVG; -.
DR PhylomeDB; P0CI79; -.
DR BioCyc; BSUB:BSU17680-MON; -.
DR BRENDA; 2.1.1.45; 658.
DR SABIO-RK; P0CI79; -.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; P0CI79; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004799; F:thymidylate synthase activity; IDA:CACAO.
DR GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central.
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..279
FT /note="Thymidylate synthase 1"
FT /id="PRO_0000140931"
FT ACT_SITE 161
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00008"
FT BINDING 141..142
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 181..184
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 184
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 192
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 222..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 278
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 VARIANT 84..85
FT /note="ND -> TE (in strain: ATCC 6633)"
FT VARIANT 88
FT /note="M -> K (in strain: ATCC 6633)"
FT VARIANT 118
FT /note="S -> N (in strain: ATCC 6633)"
FT VARIANT 155
FT /note="A -> S (in strain: ATCC 6633)"
FT VARIANT 171
FT /note="H -> Q (in strain: ATCC 6633)"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:1BSF"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 40..50
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 65..76
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 83..87
FT /evidence="ECO:0007829|PDB:1BKP"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:1BKO"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:1BSF"
FT HELIX 109..113
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 126..136
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:1BKP"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 161..170
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 173..184
FT /evidence="ECO:0007829|PDB:1BKP"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 189..207
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 210..224
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 228..236
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:1BKP"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:1BKP"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:1BKP"
SQ SEQUENCE 279 AA; 32807 MW; CC0B127AAF7912BD CRC64;
MTQFDKQYNS IIKDIINNGI SDEEFDVRTK WDSDGTPAHT LSVISKQMRF DNSEVPILTT
KKVAWKTAIK ELLWIWQLKS NDVNDLNMMG VHIWDQWKQE DGTIGHAYGF QLGKKNRSLN
GEKVDQVDYL LHQLKNNPSS RRHITMLWNP DELDAMALTP CVYETQWYVK HGKLHLEVRA
RSNDMALGNP FNVFQYNVLQ RMIAQVTGYE LGEYIFNIGD CHVYTRHIDN LKIQMEREQF
EAPELWINPE VKDFYDFTID DFKLINYKHG DKLLFEVAV
