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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.

Catalytic activityi

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

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 – 4031By similarity
Binding sitei404 – 4041dUMP
Binding sitei434 – 4341dUMP

Regions

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

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 synthasePRO_0000186354Add
BLAST

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

1
521
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi2 – 43Combined sources
Turni10 – 134Combined sources
Helixi14 – 163Combined sources
Beta strandi23 – 308Combined sources
Beta strandi33 – 397Combined sources
Helixi46 – 5712Combined sources
Beta strandi60 – 634Combined sources
Beta strandi70 – 778Combined sources
Helixi78 – 825Combined sources
Helixi86 – 883Combined sources
Beta strandi94 – 996Combined sources
Helixi105 – 1106Combined sources
Beta strandi112 – 1143Combined sources
Helixi115 – 1217Combined sources
Helixi122 – 1243Combined sources
Beta strandi125 – 1306Combined sources
Helixi132 – 1398Combined sources
Turni142 – 1476Combined sources
Beta strandi148 – 1536Combined sources
Helixi157 – 1637Combined sources
Helixi168 – 1714Combined sources
Beta strandi172 – 1809Combined sources
Beta strandi188 – 1903Combined sources
Helixi199 – 2013Combined sources
Beta strandi206 – 2116Combined sources
Beta strandi218 – 2214Combined sources
Beta strandi224 – 2329Combined sources
Helixi235 – 25016Combined sources
Beta strandi252 – 2554Combined sources
Beta strandi261 – 27313Combined sources
Helixi275 – 2773Combined sources
Beta strandi283 – 2853Combined sources
Helixi289 – 30012Combined sources
Helixi307 – 3104Combined sources
Turni311 – 3133Combined sources
Turni319 – 3213Combined sources
Helixi323 – 3286Combined sources
Helixi343 – 3497Combined sources
Beta strandi357 – 3593Combined sources
Helixi368 – 37811Combined sources
Beta strandi386 – 3883Combined sources
Turni392 – 3943Combined sources
Helixi395 – 3973Combined sources
Beta strandi398 – 4003Combined sources
Beta strandi403 – 41210Combined sources
Beta strandi415 – 42612Combined sources
Turni427 – 4293Combined sources
Helixi430 – 44819Combined sources
Beta strandi452 – 46615Combined sources
Helixi467 – 4693Combined sources
Helixi470 – 4767Combined sources
Beta strandi486 – 4905Combined sources
Helixi496 – 4983Combined sources
Helixi501 – 5033Combined sources
Beta strandi504 – 5085Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ27793.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni237 – 521285Thymidylate 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.

Q27793-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSLFKIRMPE TVAEGTRLAL RAFSLVVAVD EHGGIGDGRS IPWNVPEDMK
60 70 80 90 100
FFRDLTTKLR GKNVKPSPAK RNAVVMGRKT WDSIPPKFRP LPGRLNVVLS
110 120 130 140 150
STLTTQHLLD GLPDEEKRNL HADSIVAVNG GLEQALRLLA SPNYTPSIET
160 170 180 190 200
VYCIGGGSVY AEALRPPCVH LLQAIYRTTI RASESSCSVF FRVPESGTEA
210 220 230 240 250
AAGIEWQRET ISEELTSANG NETKYYFEKL IPRNREEEQY LSLVDRIIRE
260 270 280 290 300
GNVKHDRTGV GTLSIFGAQM RFSLRNNRLP LLTTKRVFWR GVCEELLWFL
310 320 330 340 350
RGETYAKKLS DKGVHIWDDN GSRAFLDSRG LTEYEEMDLG PVYGFQWRHF
360 370 380 390 400
GAAYTHHDAN YDGQGVDQIK AIVETLKTNP DDRRMLFTAW NPSALPRMAL
410 420 430 440 450
PPCHLLAQFY VSNGELSCML YQRSCDMGLG VPFNIASYAL LTILIAKATG
460 470 480 490 500
LRPGELVHTL GDAHVYSNHV EPCNEQLKRV PRAFPYLVFR REREFLEDYE
510 520
EGDMEVIDYA PYPPISMKMA V
Length:521
Mass (Da):58,853
Last modified:May 1, 1997 - v2
Checksum:iDCB9F8782855810C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L22484 Genomic DNA. Translation: AAB49898.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L22484 Genomic DNA. Translation: AAB49898.1 .

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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: November 26, 2014
This is version 78 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