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Protein

Bifunctional dihydrofolate reductase-thymidylate synthase

Gene
N/A
Organism
Trypanosoma brucei brucei
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP (By similarity).By similarity

Catalytic activityi

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.

Pathway:idTTP biosynthesis

This protein is involved in the pathway dTTP biosynthesis, which is part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the pathway dTTP biosynthesis and in Pyrimidine metabolism.

Pathway:itetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:
  1. Bifunctional dihydrofolate reductase-thymidylate synthase
This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei32 – 321Substrate; via carbonyl oxygenBy similarity
Binding sitei34 – 341NADP; via amide nitrogen and carbonyl oxygenBy similarity
Binding sitei54 – 541SubstrateBy similarity
Binding sitei160 – 1601Substrate; via carbonyl oxygenBy similarity
Binding sitei166 – 1661SubstrateBy similarity
Binding sitei184 – 1841SubstrateBy similarity
Binding sitei263 – 2631dUMPBy similarity
Active sitei409 – 4091By similarity
Binding sitei410 – 4101dUMPBy similarity
Binding sitei440 – 4401dUMPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi40 – 467NADPBy similarity
Nucleotide bindingi84 – 863NADPBy similarity
Nucleotide bindingi105 – 1084NADPBy similarity
Nucleotide bindingi161 – 1688NADPBy similarity
Nucleotide bindingi428 – 4325dUMPBy similarity
Nucleotide bindingi470 – 4723dUMPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Oxidoreductase, Transferase

Keywords - Biological processi

Nucleotide biosynthesis, One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
UPA00575.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase
Short name:
DHFR-TS
Including the following 2 domains:
Dihydrofolate reductase (EC:1.5.1.3)
Thymidylate synthase (EC:2.1.1.45)
OrganismiTrypanosoma brucei brucei
Taxonomic identifieri5702 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosoma

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 527527Bifunctional dihydrofolate reductase-thymidylate synthasePRO_0000186353Add
BLAST

Interactioni

Subunit structurei

Homodimer.By similarity

Structurei

Secondary structure

1
527
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi29 – 368Combined sources
Beta strandi40 – 467Combined sources
Helixi52 – 6312Combined sources
Beta strandi66 – 694Combined sources
Beta strandi76 – 838Combined sources
Helixi84 – 896Combined sources
Helixi92 – 943Combined sources
Beta strandi100 – 1056Combined sources
Helixi111 – 1155Combined sources
Helixi121 – 1277Combined sources
Helixi128 – 1303Combined sources
Beta strandi131 – 1366Combined sources
Helixi138 – 1447Combined sources
Helixi148 – 1536Combined sources
Beta strandi154 – 1596Combined sources
Helixi163 – 1697Combined sources
Helixi174 – 1774Combined sources
Beta strandi178 – 18811Combined sources
Beta strandi212 – 2176Combined sources
Beta strandi230 – 2389Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QFXX-ray2.20A/B1-241[»]
3RG9X-ray2.00A/B1-240[»]
ProteinModelPortaliQ27783.
SMRiQ27783. Positions 11-521.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ27783.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 238211DHFRAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni243 – 527285Thymidylate synthaseAdd
BLAST

Sequence similaritiesi

In the N-terminal section; belongs to the dihydrofolate reductase family.Curated
In the C-terminal section; belongs to the thymidylate synthase family.Curated

Family and domain databases

Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact.
InterProiIPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFiPIRSF000389. DHFR-TS. 1 hit.
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q27783-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSLTRILRK KIPVHELAGK ISRPPLRPFS VVVASDEKGG IGDGGTIPWE
60 70 80 90 100
IPEDMQYFRR VTTNLRGKNV KPSPSKRNAV VMGRKTWDSL PPKFRPLSNR
110 120 130 140 150
LNVVLSRSAT KEQLLAGIPD PIKRAEAAND VVAVNGGLED ALRMLVSKEH
160 170 180 190 200
TSSIETVFCI GGGTIYKQAL CAPCVNVLQA IHRTVVRPAS NSCSVFFDIP
210 220 230 240 250
AAGTKTPEGL ELVRESITDE RVSTGAGGKK YQFEKLVPRN SEEEQYLNLV
260 270 280 290 300
GRIIDEGCTK CDRTGVGTRS LFGAQMRFSL RNNRLPLLTT KRVFWRGVCE
310 320 330 340 350
ELLWFLRGET NAKLLSDKGI HIWDGNGSRA FLDSRGLTDY DEMDLGPVYG
360 370 380 390 400
FQWRHFGADY ISCKVDSEGK GVDQIANIVK SLIENPDDRR MICTAWNPAA
410 420 430 440 450
LPRMALPPCH MMAQFYVSNG ELSCMLYQRS CDMGLGVPFN IASYALLTFL
460 470 480 490 500
MAKASGLRPG ELVHTLGDAH VYSNHVEPCR KQLKRVPRPF PFIVFKQDKE
510 520
FLEDFQESDI EVIDYSPYPV ISMEMAV
Length:527
Mass (Da):58,805
Last modified:November 1, 1996 - v1
Checksum:i39982FC553BF7601
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20781 Genomic DNA. Translation: AAA91362.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20781 Genomic DNA. Translation: AAA91362.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QFXX-ray2.20A/B1-241[»]
3RG9X-ray2.00A/B1-240[»]
ProteinModelPortaliQ27783.
SMRiQ27783. Positions 11-521.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
UPA00575.

Miscellaneous databases

EvolutionaryTraceiQ27783.

Family and domain databases

Gene3Di3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact.
InterProiIPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFiPIRSF000389. DHFR-TS. 1 hit.
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Trypanosoma brucei dihydrofolate reductase-thymidylate synthase: gene isolation and expression and characterization of the enzyme."
    Gamarro F., Yu P.L., Zhao J., Edman U., Greene P.J., Santi D.
    Mol. Biochem. Parasitol. 72:11-22(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 427.

Entry informationi

Entry nameiDRTS_TRYBB
AccessioniPrimary (citable) accession number: Q27783
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 22, 2015
This is version 85 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure, Multifunctional enzyme

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.