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Q27793 (DRTS_TRYCR) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase

Short name=DHFR-TS

Including the following 2 domains:

  1. Dihydrofolate reductase
    EC=1.5.1.3
  2. Thymidylate synthase
    EC=2.1.1.45
OrganismTrypanosoma cruzi
Taxonomic identifier5693 [NCBI]
Taxonomic lineageEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosomaSchizotrypanum

Protein attributes

Sequence length521 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. HAMAP-Rule MF_00008

Catalytic activity

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH. Ref.3 Ref.5

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP. Ref.3 Ref.5

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. HAMAP-Rule MF_00008

Subunit structure

Homodimer. Ref.4

Sequence similarities

In the N-terminal section; belongs to the dihydrofolate reductase family.

In the C-terminal section; belongs to the thymidylate synthase family.

Contains 1 DHFR (dihydrofolate reductase) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 521521Bifunctional dihydrofolate reductase-thymidylate synthase HAMAP-Rule MF_00008
PRO_0000186354

Regions

Domain22 – 232211DHFR
Nucleotide binding34 – 407NADP HAMAP-Rule MF_00008
Nucleotide binding78 – 803NADP HAMAP-Rule MF_00008
Nucleotide binding99 – 1024NADP HAMAP-Rule MF_00008
Nucleotide binding155 – 1628NADP HAMAP-Rule MF_00008
Nucleotide binding422 – 4265dUMP HAMAP-Rule MF_00008
Nucleotide binding464 – 4663dUMP HAMAP-Rule MF_00008
Region237 – 521285Thymidylate synthase HAMAP-Rule MF_00008

Sites

Active site4031 By similarity
Binding site261Substrate; via carbonyl oxygen
Binding site281NADP; via amide nitrogen and carbonyl oxygen
Binding site481Substrate
Binding site1541Substrate; via carbonyl oxygen
Binding site1601Substrate
Binding site1781Substrate
Binding site2571dUMP
Binding site4041dUMP
Binding site4341dUMP

Secondary structure

................................................................................................ 521
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q27793 [UniParc].

Last modified May 1, 1997. Version 2.
Checksum: DCB9F8782855810C

FASTA52158,853
        10         20         30         40         50         60 
MSLFKIRMPE TVAEGTRLAL RAFSLVVAVD EHGGIGDGRS IPWNVPEDMK FFRDLTTKLR 

        70         80         90        100        110        120 
GKNVKPSPAK RNAVVMGRKT WDSIPPKFRP LPGRLNVVLS STLTTQHLLD GLPDEEKRNL 

       130        140        150        160        170        180 
HADSIVAVNG GLEQALRLLA SPNYTPSIET VYCIGGGSVY AEALRPPCVH LLQAIYRTTI 

       190        200        210        220        230        240 
RASESSCSVF FRVPESGTEA AAGIEWQRET ISEELTSANG NETKYYFEKL IPRNREEEQY 

       250        260        270        280        290        300 
LSLVDRIIRE GNVKHDRTGV GTLSIFGAQM RFSLRNNRLP LLTTKRVFWR GVCEELLWFL 

       310        320        330        340        350        360 
RGETYAKKLS DKGVHIWDDN GSRAFLDSRG LTEYEEMDLG PVYGFQWRHF GAAYTHHDAN 

       370        380        390        400        410        420 
YDGQGVDQIK AIVETLKTNP DDRRMLFTAW NPSALPRMAL PPCHLLAQFY VSNGELSCML 

       430        440        450        460        470        480 
YQRSCDMGLG VPFNIASYAL LTILIAKATG LRPGELVHTL GDAHVYSNHV EPCNEQLKRV 

       490        500        510        520 
PRAFPYLVFR REREFLEDYE EGDMEVIDYA PYPPISMKMA V 

« Hide

References

[1]"Cloning and expression of the dihydrofolate reductase-thymidylate synthase gene from Trypanosoma cruzi."
Reche P., Arrebola R., Olmo A., Santi D.V., Gonzalez-Pacanowska D., Ruiz-Perez L.M.
Mol. Biochem. Parasitol. 65:247-258(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Y.
[2]"Expression and characterization of the Trypanosoma cruzi dihydrofolate reductase domain."
Reche P., Arrebola R., Santi D.V., Gonzalez-Pacanowska D., Ruiz-Perez L.M.
Mol. Biochem. Parasitol. 76:175-185(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Y.
[3]"Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function."
Schormann N., Senkovich O., Walker K., Wright D.L., Anderson A.C., Rosowsky A., Ananthan S., Shinkre B., Velu S., Chattopadhyay D.
Proteins 73:889-901(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEXES WITH NADP; METHOTREXATE AND TRIMETREXATE, CATALYTIC ACTIVITY.
[4]"Structures of dihydrofolate reductase-thymidylate synthase of Trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexate."
Senkovich O., Schormann N., Chattopadhyay D.
Acta Crystallogr. D 65:704-716(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEXES WITH NADP; UMP; METHOTREXATE AND TRIMETREXATE, SUBUNIT.
[5]"Crystallization and preliminary crystallographic studies of dihydrofolate reductase-thymidylate synthase from Trypanosoma cruzi, the Chagas disease pathogen."
Chitnumsub P., Yuvaniyama J., Chahomchuen T., Vilaivan T., Yuthavong Y.
Acta Crystallogr. F 65:1175-1178(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEXES WITH NADP; UMP AND THE SYNTHETIC INHIBITORS C-448; CYC AND Q-8, CATALYTIC ACTIVITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L22484 Genomic DNA. Translation: AAB49898.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2H2QX-ray2.40A/B1-521[»]
3CL9X-ray3.30A1-521[»]
3CLBX-ray3.00A/B/C/D1-521[»]
3HBBX-ray3.00A/B/C/D1-521[»]
3INVX-ray2.37A/B1-521[»]
3IRMX-ray2.10A/B/C/D1-521[»]
3IRNX-ray2.60A/B/C/D1-521[»]
3IROX-ray2.80A/B/C/D1-521[»]
ProteinModelPortalQ27793.
SMRQ27793. Positions 2-515.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ27793.
ChEMBLCHEMBL1163130.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPMF_00008. Thymidy_synth_bact.
InterProIPR024072. 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]
PfamPF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PIRSFPIRSF000389. DHFR-TS. 1 hit.
PRINTSPR00108. THYMDSNTHASE.
SUPFAMSSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsTIGR03284. thym_sym. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ27793.

Entry information

Entry nameDRTS_TRYCR
AccessionPrimary (citable) accession number: Q27793
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: February 19, 2014
This is version 76 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways