DRTS_TOXGO
ID DRTS_TOXGO Reviewed; 610 AA.
AC Q07422;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 121.
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 Toxoplasma gondii.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia;
OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma.
OX NCBI_TaxID=5811;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=RH;
RX PubMed=8454599; DOI=10.1016/s0021-9258(18)53249-x;
RA Roos D.S.;
RT "Primary structure of the dihydrofolate reductase-thymidylate synthase gene
RT from Toxoplasma gondii.";
RL J. Biol. Chem. 268:6269-6280(1993).
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 -!- 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; L08489; AAB00163.1; -; Genomic_DNA.
DR PIR; A46005; A46005.
DR PDB; 4ECK; X-ray; 3.52 A; A/B=1-610.
DR PDB; 4EIL; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-610.
DR PDB; 4KY4; X-ray; 2.79 A; A/B/C/D/E/F/G/H=1-610.
DR PDB; 4KYA; X-ray; 3.26 A; A/B/C/D/E/F/G/H=1-610.
DR PDB; 5T0L; X-ray; 3.13 A; A/B=1-610.
DR PDB; 6AOG; X-ray; 3.20 A; A/B=1-610.
DR PDB; 6AOH; X-ray; 3.50 A; A/B=1-610.
DR PDB; 6AOI; X-ray; 2.97 A; A/B=1-610.
DR PDB; 6N1S; X-ray; 3.00 A; A/B=1-610.
DR PDB; 6N1T; X-ray; 3.50 A; A/B=1-610.
DR PDBsum; 4ECK; -.
DR PDBsum; 4EIL; -.
DR PDBsum; 4KY4; -.
DR PDBsum; 4KYA; -.
DR PDBsum; 5T0L; -.
DR PDBsum; 6AOG; -.
DR PDBsum; 6AOH; -.
DR PDBsum; 6AOI; -.
DR PDBsum; 6N1S; -.
DR PDBsum; 6N1T; -.
DR AlphaFoldDB; Q07422; -.
DR SMR; Q07422; -.
DR BindingDB; Q07422; -.
DR ChEMBL; CHEMBL2425; -.
DR DrugCentral; Q07422; -.
DR EnsemblProtists; TGME49_249180-t26_1; TGME49_249180-t26_1; TGME49_249180.
DR VEuPathDB; ToxoDB:TGARI_249180; -.
DR VEuPathDB; ToxoDB:TGCAST_249180; -.
DR VEuPathDB; ToxoDB:TGCOUG_249180; -.
DR VEuPathDB; ToxoDB:TGDOM2_249180; -.
DR VEuPathDB; ToxoDB:TGFOU_249180; -.
DR VEuPathDB; ToxoDB:TGGT1_249180; -.
DR VEuPathDB; ToxoDB:TGMAS_249180; -.
DR VEuPathDB; ToxoDB:TGME49_249180; -.
DR VEuPathDB; ToxoDB:TGP89_249180; -.
DR VEuPathDB; ToxoDB:TGPRC2_249180; -.
DR VEuPathDB; ToxoDB:TGRH88_062920; -.
DR VEuPathDB; ToxoDB:TGRUB_249180; -.
DR VEuPathDB; ToxoDB:TGVAND_249180; -.
DR VEuPathDB; ToxoDB:TGVEG_249180; -.
DR OMA; HHKIEMK; -.
DR BRENDA; 1.5.1.3; 6411.
DR BRENDA; 2.1.1.45; 6411.
DR SABIO-RK; Q07422; -.
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 1: Evidence at protein level;
KW 3D-structure; Methyltransferase; Multifunctional enzyme; NADP;
KW Nucleotide biosynthesis; One-carbon metabolism; Oxidoreductase;
KW Transferase.
FT CHAIN 1..610
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase"
FT /id="PRO_0000186352"
FT DOMAIN 4..250
FT /note="DHFR"
FT REGION 256..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..610
FT /note="Thymidylate synthase"
FT COMPBIAS 260..282
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 489
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 10
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 16..22
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 31
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 81..83
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 102..105
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 152..159
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 344
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 490
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 509..513
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 521
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 551..553
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 29..40
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 74..80
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 81..86
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 108..114
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 130..141
FT /evidence="ECO:0007829|PDB:4EIL"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 154..163
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 166..174
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 241..250
FT /evidence="ECO:0007829|PDB:4EIL"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:4KY4"
FT HELIX 325..337
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 339..341
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 344..347
FT /evidence="ECO:0007829|PDB:6AOI"
FT STRAND 349..360
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 375..386
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 393..396
FT /evidence="ECO:0007829|PDB:4EIL"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 409..414
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 429..435
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:6AOH"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:4KYA"
FT HELIX 454..464
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 472..474
FT /evidence="ECO:0007829|PDB:4EIL"
FT TURN 478..480
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 481..483
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 489..497
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 501..513
FT /evidence="ECO:0007829|PDB:4EIL"
FT TURN 514..516
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 517..535
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 539..553
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 557..563
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 573..577
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 579..581
FT /evidence="ECO:0007829|PDB:4EIL"
FT HELIX 585..587
FT /evidence="ECO:0007829|PDB:4EIL"
FT STRAND 592..597
FT /evidence="ECO:0007829|PDB:4EIL"
SQ SEQUENCE 610 AA; 68752 MW; CFAF564416D04A29 CRC64;
MQKPVCLVVA MTPKRGIGIN NGLPWPHLTT DFKHFSRVTK TTPEEASRLN GWLPRKFAKT
GDSGLPSPSV GKRFNAVVMG RKTWESMPRK FRPLVDRLNI VVSSSLKEED IAAEKPQAEG
QQRVRVCASL PAALSLLEEE YKDSVDQIFV VGGAGLYEAA LSLGVASHLY ITRVAREFPC
DVFFPAFPGD DILSNKSTAA QAAAPAESVF VPFCPELGRE KDNEATYRPI FISKTFSDNG
VPYDFVVLEK RRKTDDAATA EPSNAMSSLT STRETTPVHG LQAPSSAAAI APVLAWMDEE
DRKKREQKEL IRAVPHVHFR GHEEFQYLDL IADIINNGRT MDDRTGVGVI SKFGCTMRYS
LDQAFPLLTT KRVFWKGVLE ELLWFIRGDT NANHLSEKGV KIWDKNVTRE FLDSRNLPHR
EVGDIGPGYG FQWRHFGAAY KDMHTDYTGQ GVDQLKNVIQ MLRTNPTDRR MLMTAWNPAA
LDEMALPPCH LLCQFYVNDQ KELSCIMYQR SCDVGLGVPF NIASYSLLTL MVAHVCNLKP
KEFIHFMGNT HVYTNHVEAL KEQLRREPRP FPIVNILNKE RIKEIDDFTA EDFEVVGYVP
HGRIQMEMAV
