DRTS_PLABA
ID DRTS_PLABA Reviewed; 587 AA.
AC Q27713; Q27714;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase;
DE Short=DHFR-TS;
DE Includes:
DE RecName: Full=Dihydrofolate reductase;
DE EC=1.5.1.3;
DE Includes:
DE RecName: Full=Thymidylate synthase;
DE EC=2.1.1.45;
OS Plasmodium berghei (strain Anka).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Vinckeia).
OX NCBI_TaxID=5823;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7891743; DOI=10.1016/0166-6851(94)00163-4;
RA van Dijk M.R., McConkey G.A., Vinkenoog R., Waters A.P., Janse C.J.;
RT "Mechanisms of pyrimethamine resistance in two different strains of
RT Plasmodium berghei.";
RL Mol. Biochem. Parasitol. 68:167-171(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 12-201.
RX PubMed=7969277; DOI=10.1016/0166-6851(94)90087-6;
RA Cheng Q., Saul A.;
RT "The dihydrofolate reductase domain of rodent malarias: point mutations and
RT pyrimethamine resistance.";
RL Mol. Biochem. Parasitol. 65:361-363(1994).
CC -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis.
CC Key enzyme in folate metabolism. Catalyzes an essential reaction for de
CC novo glycine and purine synthesis, DNA precursor synthesis, and for the
CC conversion of dUMP to dTMP (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3;
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;
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC reductase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC synthase family. {ECO:0000305}.
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DR EMBL; U12275; AAB60237.1; -; Genomic_DNA.
DR EMBL; L28119; AAA29581.1; -; Genomic_DNA.
DR AlphaFoldDB; Q27713; -.
DR SMR; Q27713; -.
DR STRING; 5821.PBANKA_071930; -.
DR BindingDB; Q27713; -.
DR ChEMBL; CHEMBL3963; -.
DR DrugCentral; Q27713; -.
DR PRIDE; Q27713; -.
DR eggNOG; KOG0673; Eukaryota.
DR eggNOG; KOG1324; Eukaryota.
DR UniPathway; UPA00077; UER00158.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00209; DHFR; 1.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.30.572.10; -; 1.
DR Gene3D; 3.40.430.10; -; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR012262; DHFR-TS.
DR InterPro; IPR017925; DHFR_CS.
DR InterPro; IPR001796; DHFR_dom.
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; PF00186; DHFR_1; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PIRSF; PIRSF000389; DHFR-TS; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF53597; SSF53597; 1.
DR SUPFAM; SSF55831; SSF55831; 1.
DR TIGRFAMs; TIGR03284; thym_sym; 1.
DR PROSITE; PS00075; DHFR_1; 1.
DR PROSITE; PS51330; DHFR_2; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Methyltransferase; Multifunctional enzyme; NADP; Nucleotide biosynthesis;
KW One-carbon metabolism; Oxidoreductase; Transferase.
FT CHAIN 1..587
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase"
FT /id="PRO_0000186347"
FT DOMAIN 9..237
FT /note="DHFR"
FT REGION 301..587
FT /note="Thymidylate synthase"
FT ACT_SITE 469
FT /evidence="ECO:0000250"
FT BINDING 36..42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 51
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 108..110
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 129..132
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 174..181
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 324
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 470
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 488..492
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 500
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 530..532
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT VARIANT 110
FT /note="S -> N (in pyrimethamine resistance)"
FT VARIANT 177
FT /note="S -> F (in pyrimethamine resistance)"
SQ SEQUENCE 587 AA; 68932 MW; 6E638C2B02FEC13A CRC64;
MEDLSETFDI YAICACCKVL NDDEKVRCFN NKTFKGIGNA GVLPWKCNLI DMKYFSSVTS
YINENNYIRL KWKRDKYMEK HNLKNNVELN TNIISSTNNL QNIVVMGKKS WESIPKKFKP
LQNRINIILS RTLKKEDIVN ENNNENNNVI IIKSVDDLFP ILKCTKYYKC FIIGGSSVYK
EFLDRNLIKK IYFTRINNSY NCDVLFPEIN ENLFKITSIS DVYYSNNTTL DFIIYSKTKE
INPNEEVPNN TFLGVCDEQN KAFDDEDDYT YFSFNKNKEN IKKNSEHAHN FKIYNSIKYK
NHPEYQYLNI IYDIIMHGNK QDDRTGVGVL SKFGYMMKFN LNEYFPLLTT KKLFIRGIIE
ELLWFIRGET NGNTLLEKNV RIWEANGTRE FLDNRKLFHR EVNDLGPIYG FQWRHFGAEY
TDMHDNYKDK GVDQLKNIIN LIKNDPTCRR IILCAWNVKN LDQMALPPCH ILCQFYVFDG
KLSCIMYQRS CDLGLGVPFN IASYSIFTYM IAQVCNLQAA EFIHVLGNAH VYNNHIESLK
IQLNRTPYPF PTLKLNPDIK NIEDFTISDF TVQNYVHHDK INMDMAA
