TYSY_BRUME
ID TYSY_BRUME Reviewed; 264 AA.
AC P67042; Q8YI37;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 92.
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=BMEI0608;
OS Brucella melitensis biotype 1 (strain 16M / ATCC 23456 / NCTC 10094).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Brucellaceae; Brucella/Ochrobactrum group; Brucella.
OX NCBI_TaxID=224914;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=16M / ATCC 23456 / NCTC 10094;
RX PubMed=11756688; DOI=10.1073/pnas.221575398;
RA DelVecchio V.G., Kapatral V., Redkar R.J., Patra G., Mujer C., Los T.,
RA Ivanova N., Anderson I., Bhattacharyya A., Lykidis A., Reznik G.,
RA Jablonski L., Larsen N., D'Souza M., Bernal A., Mazur M., Goltsman E.,
RA Selkov E., Elzer P.H., Hagius S., O'Callaghan D., Letesson J.-J.,
RA Haselkorn R., Kyrpides N.C., Overbeek R.;
RT "The genome sequence of the facultative intracellular pathogen Brucella
RT melitensis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:443-448(2002).
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; AE008917; AAL51789.1; -; Genomic_DNA.
DR PIR; AB3328; AB3328.
DR RefSeq; WP_002964508.1; NZ_GG703780.1.
DR PDB; 3IX6; X-ray; 2.20 A; A/B=1-264.
DR PDBsum; 3IX6; -.
DR AlphaFoldDB; P67042; -.
DR SMR; P67042; -.
DR STRING; 224914.BMEI0608; -.
DR EnsemblBacteria; AAL51789; AAL51789; BMEI0608.
DR GeneID; 45052414; -.
DR KEGG; bme:BMEI0608; -.
DR PATRIC; fig|224914.52.peg.857; -.
DR eggNOG; COG0207; Bacteria.
DR OMA; KQYLDLC; -.
DR PhylomeDB; P67042; -.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; P67042; -.
DR Proteomes; UP000000419; Chromosome I.
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; Methyltransferase; Nucleotide biosynthesis;
KW Transferase.
FT CHAIN 1..264
FT /note="Thymidylate synthase"
FT /id="PRO_0000140942"
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:3IX6"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 26..37
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 52..64
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 111..121
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 146..155
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 158..169
FT /evidence="ECO:0007829|PDB:3IX6"
FT TURN 170..173
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 174..192
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 195..209
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:3IX6"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:3IX6"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:3IX6"
SQ SEQUENCE 264 AA; 30330 MW; FECAD558B5EDCAFA CRC64;
MRTYLDLLQH VLDHGVDRDD RTGTGTRSVF GYQMRFDLEE GFPVLTTKKL HLRSIIHELL
WFLKGDTNIA YLKENGVTIW DEWADENGDL GPVYGYQWRS WPAPDGRHID QIANLLKMLH
TNPQSRRLIV SAWNPALVDE MALPPCHCLF QFYVANGRLS CQLYQRSADI FLGVPFNIAS
YALLTMMIAQ VTGLKPGEFI HTLGDAHIYS NHFEQARLQL TRTPKKLPVM HINPDVKDLF
AFRFEDFRLD GYEADPTIKA PIAV
