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Q27793

- DRTS_TRYCR

UniProt

Q27793 - DRTS_TRYCR

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Protein
Bifunctional dihydrofolate reductase-thymidylate synthase
Gene
N/A
Organism
Trypanosoma cruzi
Status
Reviewed - Annotation score: 5 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.UniRule annotation

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.2 Publications
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.2 Publications

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei26 – 261Substrate; via carbonyl oxygen
Binding sitei28 – 281NADP; via amide nitrogen and carbonyl oxygen
Binding sitei48 – 481Substrate
Binding sitei154 – 1541Substrate; via carbonyl oxygen
Binding sitei160 – 1601Substrate
Binding sitei178 – 1781Substrate
Binding sitei257 – 2571dUMP
Active sitei403 – 4031 By similarity
Binding sitei404 – 4041dUMP
Binding sitei434 – 4341dUMP

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi34 – 407NADPUniRule annotation
Nucleotide bindingi78 – 803NADPUniRule annotation
Nucleotide bindingi99 – 1024NADPUniRule annotation
Nucleotide bindingi155 – 1628NADPUniRule annotation
Nucleotide bindingi422 – 4265dUMPUniRule annotation
Nucleotide bindingi464 – 4663dUMPUniRule annotation

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB-EC
  2. thymidylate synthase activity Source: UniProtKB-EC

GO - Biological processi

  1. dTMP biosynthetic process Source: InterPro
  2. glycine biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
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.

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 cruzi
Taxonomic identifieri5693 [NCBI]
Taxonomic lineageiEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosomaSchizotrypanum

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 521521Bifunctional dihydrofolate reductase-thymidylate synthaseUniRule annotation
PRO_0000186354Add
BLAST

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi2 – 43
Turni10 – 134
Helixi14 – 163
Beta strandi23 – 308
Beta strandi33 – 397
Helixi46 – 5712
Beta strandi60 – 634
Beta strandi70 – 778
Helixi78 – 825
Helixi86 – 883
Beta strandi94 – 996
Helixi105 – 1106
Beta strandi112 – 1143
Helixi115 – 1217
Helixi122 – 1243
Beta strandi125 – 1306
Helixi132 – 1398
Turni142 – 1476
Beta strandi148 – 1536
Helixi157 – 1637
Helixi168 – 1714
Beta strandi172 – 1809
Beta strandi188 – 1903
Helixi199 – 2013
Beta strandi206 – 2116
Beta strandi218 – 2214
Beta strandi224 – 2329
Helixi235 – 25016
Beta strandi252 – 2554
Beta strandi261 – 27313
Helixi275 – 2773
Beta strandi283 – 2853
Helixi289 – 30012
Helixi307 – 3104
Turni311 – 3133
Turni319 – 3213
Helixi323 – 3286
Helixi343 – 3497
Beta strandi357 – 3593
Helixi368 – 37811
Beta strandi386 – 3883
Turni392 – 3943
Helixi395 – 3973
Beta strandi398 – 4003
Beta strandi403 – 41210
Beta strandi415 – 42612
Turni427 – 4293
Helixi430 – 44819
Beta strandi452 – 46615
Helixi467 – 4693
Helixi470 – 4767
Beta strandi486 – 4905
Helixi496 – 4983
Helixi501 – 5033
Beta strandi504 – 5085

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ27793.
SMRiQ27793. Positions 2-515.

Miscellaneous databases

EvolutionaryTraceiQ27793.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 232211DHFR
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni237 – 521285Thymidylate synthaseUniRule annotation
Add
BLAST

Sequence similaritiesi

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

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.

Q27793-1 [UniParc]FASTAAdd to Basket

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MSLFKIRMPE TVAEGTRLAL RAFSLVVAVD EHGGIGDGRS IPWNVPEDMK    50
FFRDLTTKLR GKNVKPSPAK RNAVVMGRKT WDSIPPKFRP LPGRLNVVLS 100
STLTTQHLLD GLPDEEKRNL HADSIVAVNG GLEQALRLLA SPNYTPSIET 150
VYCIGGGSVY AEALRPPCVH LLQAIYRTTI RASESSCSVF FRVPESGTEA 200
AAGIEWQRET ISEELTSANG NETKYYFEKL IPRNREEEQY LSLVDRIIRE 250
GNVKHDRTGV GTLSIFGAQM RFSLRNNRLP LLTTKRVFWR GVCEELLWFL 300
RGETYAKKLS DKGVHIWDDN GSRAFLDSRG LTEYEEMDLG PVYGFQWRHF 350
GAAYTHHDAN YDGQGVDQIK AIVETLKTNP DDRRMLFTAW NPSALPRMAL 400
PPCHLLAQFY VSNGELSCML YQRSCDMGLG VPFNIASYAL LTILIAKATG 450
LRPGELVHTL GDAHVYSNHV EPCNEQLKRV PRAFPYLVFR REREFLEDYE 500
EGDMEVIDYA PYPPISMKMA V 521
Length:521
Mass (Da):58,853
Last modified:May 1, 1997 - v2
Checksum:iDCB9F8782855810C
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L22484 Genomic DNA. Translation: AAB49898.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L22484 Genomic DNA. Translation: AAB49898.1 .

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2H2Q X-ray 2.40 A/B 1-521 [» ]
3CL9 X-ray 3.30 A 1-521 [» ]
3CLB X-ray 3.00 A/B/C/D 1-521 [» ]
3HBB X-ray 3.00 A/B/C/D 1-521 [» ]
3INV X-ray 2.37 A/B 1-521 [» ]
3IRM X-ray 2.10 A/B/C/D 1-521 [» ]
3IRN X-ray 2.60 A/B/C/D 1-521 [» ]
3IRO X-ray 2.80 A/B/C/D 1-521 [» ]
ProteinModelPortali Q27793.
SMRi Q27793. Positions 2-515.
ModBasei Search...
MobiDBi Search...

Chemistry

BindingDBi Q27793.
ChEMBLi CHEMBL1163130.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .

Miscellaneous databases

EvolutionaryTracei Q27793.

Family and domain databases

Gene3Di 3.30.572.10. 1 hit.
3.40.430.10. 1 hit.
HAMAPi MF_00008. Thymidy_synth_bact.
InterProi IPR024072. 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 ]
Pfami PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view ]
PIRSFi PIRSF000389. DHFR-TS. 1 hit.
PRINTSi PR00108. THYMDSNTHASE.
SUPFAMi SSF53597. SSF53597. 1 hit.
SSF55831. SSF55831. 1 hit.
TIGRFAMsi TIGR03284. thym_sym. 1 hit.
PROSITEi PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiDRTS_TRYCR
AccessioniPrimary (citable) accession number: Q27793
Entry historyi
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 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

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