DRTS_LEIAM
ID DRTS_LEIAM Reviewed; 520 AA.
AC P16126;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 107.
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 Leishmania amazonensis.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5659;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=MHOM/BR/77/LTB0016/C1S1;
RX PubMed=2339068; DOI=10.1093/nar/18.9.2819;
RA Nelson K., Alonso G., Langer P.J., Beverley S.M.;
RT "Sequence of the dihydrofolate reductase-thymidylate synthase (DHFR-TS)
RT gene of Leishmania amazonensis.";
RL Nucleic Acids Res. 18:2819-2819(1990).
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; X51735; CAA36020.1; -; Genomic_DNA.
DR PIR; S15756; RDLNTZ.
DR AlphaFoldDB; P16126; -.
DR SMR; P16126; -.
DR VEuPathDB; TriTrypDB:LAMA_000016400; -.
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..520
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase"
FT /id="PRO_0000186344"
FT DOMAIN 26..229
FT /note="DHFR"
FT REGION 234..520
FT /note="Thymidylate synthase"
FT ACT_SITE 400
FT /evidence="ECO:0000250"
FT BINDING 30
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 32
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 38..44
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 52
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 157..164
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 162
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 254
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 401
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 421..425
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 433
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 463..465
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
SQ SEQUENCE 520 AA; 58610 MW; B59CEE0CC3CF7BED CRC64;
MSRAAAKFKI PMPVTKADFA FPSLRAFSIV VALDKQHGIG DGESIPWRVP EDMAFFKDQT
TLLRNKKPPT DKKRNAVVMG RKTWESVPVK FRPLKGRLNV VLSSKATVEE LLAPLPEEKR
AAAAQDIVVV NGGLAAAVRL LARPPYCSSI ETAYCVGGAQ VYADAMLSPC VEKLQEVYLT
RIHTTAPACT RFFPFPPENA ATAWDLASSQ GRRKSAVDGL EFEICKYVPR NHEERQYLEL
IDRIMKTGIA KEDRTGVGTL SLFGAQMRFS LRDNRLPLLT TKRVFWRGVC EELLWFLRGE
TNAQLLADKD IHIWDGNGSR EFLDSRGLTE NTEMDLGPVY GFQWRHFGAE YRGLEANYDG
EGVDQIKFIV ETIKANPNDR RLLFTAWNPC ALHKMALPPC HLLAQFYVNT EKSELSCMLY
QRSCDMGLGV PFNIASYALL TILIAKATGL RPGELVHTLG DAHVYRSHID ALKAQLERVP
HAFPTLVFKE ERQFLEDYEL MDMEVIDYVP HPPIKMEMAV
