ID Q8MXB7_LEITR Unreviewed; 520 AA.
AC Q8MXB7;
DT 01-OCT-2002, integrated into UniProtKB/TrEMBL.
DT 01-OCT-2002, sequence version 1.
DT 27-MAR-2024, entry version 98.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|ARBA:ARBA00019798, ECO:0000256|PIRNR:PIRNR000389};
GN Name=dhfr-ts {ECO:0000313|EMBL:AAM88660.1};
OS Leishmania tropica.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5666 {ECO:0000313|EMBL:AAM88660.1};
RN [1] {ECO:0000313|EMBL:AAM88660.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Leishmania tropica var. 7 {ECO:0000313|EMBL:AAM88660.1};
RA Toydemir R.M., Akman L., Chang K.-P.;
RT "DNA sequence evidence of heterozygosity of Leishmania tropica.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
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. {ECO:0000256|ARBA:ARBA00025154}.
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:0000256|ARBA:ARBA00001707};
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 Evidence={ECO:0000256|ARBA:ARBA00001315};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC {ECO:0000256|ARBA:ARBA00004903, ECO:0000256|PIRNR:PIRNR000389}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC synthase family. {ECO:0000256|ARBA:ARBA00006900,
CC ECO:0000256|PIRNR:PIRNR000389}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC reductase family. {ECO:0000256|ARBA:ARBA00010176,
CC ECO:0000256|PIRNR:PIRNR000389}.
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DR EMBL; AF289073; AAM88660.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8MXB7; -.
DR SMR; Q8MXB7; -.
DR VEuPathDB; TriTrypDB:LTRL590_060014000; -.
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; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 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 NCBIfam; TIGR03284; thym_sym; 1.
DR PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1.
DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PIRSF; PIRSF000389; DHFR-TS; 2.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 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 {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW NADP {ECO:0000256|ARBA:ARBA00022857};
KW Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727,
KW ECO:0000256|PIRNR:PIRNR000389};
KW One-carbon metabolism {ECO:0000256|ARBA:ARBA00022563,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000389}.
FT DOMAIN 26..229
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT ACT_SITE 400
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
SQ SEQUENCE 520 AA; 58798 MW; AEBF611ED857F930 CRC64;
MSRAAARFKI LMPETKADFA FPSLRAFSIV VALDKQHGIG DGESIPWRVP EDMAFFKDQT
TLLRNKKPPT EKKRNAVVMG RKTWESVPVK FRPLKGRLNI VLSSKATVEE LLAPLPEEKR
AAAEQDVVVV NGGLAEALRL LARPPYCSSI ETAYCVGGAQ VYADAMLSPC VEKLQEVYLT
RIYTTAPACT RFFPFPPENA ATAWDLASSQ GRRKSEAEGL EFEICKYVPR NHEERQYLEL
IDRIMKTGIV KEDRTGVGTI SLFGAQMRFS LRGNRLPLLT TKRVFWRGVC EELLWFLRGE
TNARLLADKD IHIWDGNGSR EFLDSRGLTE NKEMDLGPVY GFQWRHFGAD YKGFEANYDG
EGVDQIRFIV ETIKANPNDR RLLVTAWNPC ALQKMALPPC HLLAQFYVNT DTSELSCMLY
QRSCDMGLGV PFNIASYALL TILIAKATGL RPGELVHTLG DAHVYRNHVD ALKAQLERVP
HAFPTLIFKA ERQFLEDYEL TDMEVIDYVP HPPIKMEMAL
//
