DRTS_TRYBB
ID DRTS_TRYBB Reviewed; 527 AA.
AC Q27783;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 106.
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 Trypanosoma brucei brucei.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=5702;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=427;
RX PubMed=8538681; DOI=10.1016/0166-6851(95)00059-a;
RA Gamarro F., Yu P.L., Zhao J., Edman U., Greene P.J., Santi D.;
RT "Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene
RT isolation and expression and characterization of the enzyme.";
RL Mol. Biochem. Parasitol. 72:11-22(1995).
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=(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 -!- 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 -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
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; U20781; AAA91362.1; -; Genomic_DNA.
DR PDB; 3QFX; X-ray; 2.20 A; A/B=1-241.
DR PDB; 3RG9; X-ray; 2.00 A; A/B=1-240.
DR PDBsum; 3QFX; -.
DR PDBsum; 3RG9; -.
DR AlphaFoldDB; Q27783; -.
DR SMR; Q27783; -.
DR DrugCentral; Q27783; -.
DR PRIDE; Q27783; -.
DR BRENDA; 1.5.1.3; 6519.
DR BRENDA; 2.1.1.45; 6519.
DR SABIO-RK; Q27783; -.
DR UniPathway; UPA00077; UER00158.
DR UniPathway; UPA00575; -.
DR EvolutionaryTrace; Q27783; -.
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:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
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..527
FT /note="Bifunctional dihydrofolate reductase-thymidylate
FT synthase"
FT /id="PRO_0000186353"
FT DOMAIN 28..238
FT /note="DHFR"
FT REGION 243..527
FT /note="Thymidylate synthase"
FT ACT_SITE 409
FT /evidence="ECO:0000250"
FT BINDING 32
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 40..46
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 54
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 84..86
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 105..108
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 160
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 161..168
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 166
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 263
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 410
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 428..432
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 440
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT BINDING 470..472
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /evidence="ECO:0000250"
FT STRAND 29..36
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 52..63
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 84..89
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 111..115
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 121..127
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 138..144
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 148..153
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 163..169
FT /evidence="ECO:0007829|PDB:3RG9"
FT HELIX 174..177
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 178..188
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:3RG9"
FT STRAND 230..238
FT /evidence="ECO:0007829|PDB:3RG9"
SQ SEQUENCE 527 AA; 58805 MW; 39982FC553BF7601 CRC64;
MLSLTRILRK KIPVHELAGK ISRPPLRPFS VVVASDEKGG IGDGGTIPWE IPEDMQYFRR
VTTNLRGKNV KPSPSKRNAV VMGRKTWDSL PPKFRPLSNR LNVVLSRSAT KEQLLAGIPD
PIKRAEAAND VVAVNGGLED ALRMLVSKEH TSSIETVFCI GGGTIYKQAL CAPCVNVLQA
IHRTVVRPAS NSCSVFFDIP AAGTKTPEGL ELVRESITDE RVSTGAGGKK YQFEKLVPRN
SEEEQYLNLV GRIIDEGCTK CDRTGVGTRS LFGAQMRFSL RNNRLPLLTT KRVFWRGVCE
ELLWFLRGET NAKLLSDKGI HIWDGNGSRA FLDSRGLTDY DEMDLGPVYG FQWRHFGADY
ISCKVDSEGK GVDQIANIVK SLIENPDDRR MICTAWNPAA LPRMALPPCH MMAQFYVSNG
ELSCMLYQRS CDMGLGVPFN IASYALLTFL MAKASGLRPG ELVHTLGDAH VYSNHVEPCR
KQLKRVPRPF PFIVFKQDKE FLEDFQESDI EVIDYSPYPV ISMEMAV
