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O02604

- DRTS_PLAVI

UniProt

O02604 - DRTS_PLAVI

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Protein
Bifunctional dihydrofolate reductase-thymidylate synthase
Gene
N/A
Organism
Plasmodium vivax
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.1 Publication
5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei15 – 151NADP; via amide nitrogen and carbonyl oxygen
Binding sitei53 – 531Substrate
Binding sitei153 – 1531NADP; via carbonyl oxygen
Binding sitei173 – 1731Substrate; via carbonyl oxygen
Binding sitei179 – 1791Substrate
Binding sitei194 – 1941Substrate
Binding sitei360 – 3601dUMP By similarity
Active sitei505 – 5051 By similarity
Binding sitei506 – 5061dUMP By similarity
Binding sitei536 – 5361dUMP By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi38 – 447NADPUniRule annotation
Nucleotide bindingi115 – 1173NADPUniRule annotation
Nucleotide bindingi137 – 1393NADPUniRule annotation
Nucleotide bindingi174 – 1818NADPUniRule annotation
Nucleotide bindingi524 – 5285dUMP By similarity
Nucleotide bindingi566 – 5683dUMP By similarity

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)
OrganismiPlasmodium vivax
Taxonomic identifieri5855 [NCBI]
Taxonomic lineageiEukaryotaAlveolataApicomplexaAconoidasidaHaemosporidaPlasmodiumPlasmodium (Plasmodium)

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 623623Bifunctional dihydrofolate reductase-thymidylate synthaseUniRule annotation
PRO_0000186351Add
BLAST

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 74
Beta strandi10 – 1910
Beta strandi23 – 264
Beta strandi38 – 414
Beta strandi46 – 483
Helixi51 – 6212
Helixi66 – 683
Helixi69 – 8315
Beta strandi109 – 1146
Helixi115 – 1195
Helixi123 – 1253
Beta strandi131 – 1366
Turni142 – 1443
Beta strandi150 – 1534
Helixi155 – 1639
Beta strandi170 – 1745
Helixi176 – 1849
Beta strandi189 – 20012
Beta strandi203 – 2053
Helixi211 – 2133
Beta strandi214 – 2196
Beta strandi223 – 2253
Beta strandi228 – 23710

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BL9X-ray1.90A4-238[»]
2BLAX-ray2.50A4-238[»]
2BLBX-ray3.00A4-238[»]
2BLCX-ray2.25A4-238[»]
ProteinModelPortaliO02604.
SMRiO02604. Positions 2-238, 338-623.

Miscellaneous databases

EvolutionaryTraceiO02604.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 237229DHFR
Add
BLAST
Repeati88 – 9141UniRule annotation
Repeati94 – 9742UniRule annotation
Repeati100 – 10343UniRule annotation

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni13 – 142Substrate bindingUniRule annotation
Regioni88 – 103163 X 4 AA repeats of G-G-D-NUniRule annotation
Add
BLAST
Regioni337 – 623287Thymidylate synthaseUniRule annotation
Add
BLAST

Domaini

The repeat region is missing in the pyrimethamine-resistant isolates BUR-98 and BUR-151.UniRule annotation

Sequence similaritiesi

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

Keywords - Domaini

Repeat

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.

O02604-1 [UniParc]FASTAAdd to Basket

« Hide

MEDLSDVFDI YAICACCKVA PTSEGTKNEP FSPRTFRGLG NKGTLPWKCN    50
SVDMKYFSSV TTYVDESKYE KLKWKRERYL RMEASQGGGD NTSGGDNTHG 100
GDNADKLQNV VVMGRSSWES IPKQYKPLPN RINVVLSKTL TKEDVKEKVF 150
IIDSIDDLLL LLKKLKYYKC FIIGGAQVYR ECLSRNLIKQ IYFTRINGAY 200
PCDVFFPEFD ESQFRVTSVS EVYNSKGTTL DFLVYSKVGG GVDGGASNGS 250
TATALRRTAM RSTAMRRNVA PRTAAPPMGP HSRANGERAP PRARARRTTP 300
RQRKTTSCTS ALTTKWGRKT RSTCKILKFT TASRLMQHPE YQYLGIIYDI 350
IMNGNKQGDR TGVGVMSNFG YMMKFNLSEY FPLLTTKKLF LRGIIEELLW 400
FIRGETNGNT LLNKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR 450
HFGAEYTNMH DNYEDKGVDQ LKNVIHLIKN EPTSRRIILC AWNVKDLDQM 500
ALPPCHILCQ FYVFDGKLSC IMYQRSCDLG LGVPFNIASY SIFTHMIAQV 550
CNLQPAQFIH ILGNAHVYNN HVDSLKVQLN RIPYPFPTLK LNPEVKNIED 600
FTISDFTIEN YVHHDKITME MAA 623
Length:623
Mass (Da):71,057
Last modified:May 30, 2000 - v2
Checksum:i3E6E958F04FB5828
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti58 – 581S → R in the pyrimethamine-resistant isolates BUR-98 and BUR-151; interferes with inhibitor binding.
Natural varianti117 – 1171S → N in the pyrimethamine-resistant isolates BUR-98 and BUR-151. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X98123 Genomic DNA. Translation: CAA66805.1.
PIRiJC6568.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X98123 Genomic DNA. Translation: CAA66805.1 .
PIRi JC6568.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2BL9 X-ray 1.90 A 4-238 [» ]
2BLA X-ray 2.50 A 4-238 [» ]
2BLB X-ray 3.00 A 4-238 [» ]
2BLC X-ray 2.25 A 4-238 [» ]
ProteinModelPortali O02604.
SMRi O02604. Positions 2-238, 338-623.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .

Miscellaneous databases

EvolutionaryTracei O02604.

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. "Analysis of the Plasmodium vivax dihydrofolate reductase-thymidylate synthase gene sequence."
    Eldin de Pecoulas P., Basco L.K., Tahar R., Ouatas T., Mazabraud A.
    Gene 211:177-185(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Isolate Ari/Pakistan, Isolate BUR-151 and Isolate BUR-98.
  2. "Crystal structure of dihydrofolate reductase from Plasmodium vivax: pyrimethamine displacement linked with mutation-induced resistance."
    Kongsaeree P., Khongsuk P., Leartsakulpanich U., Chitnumsub P., Tarnchompoo B., Walkinshaw M.D., Yuthavong Y.
    Proc. Natl. Acad. Sci. U.S.A. 102:13046-13051(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-238 OF WILD TYPE AND MUTANT ARG-58/ASN-117 IN COMPLEXES WITH THE SYNTHETIC INHIBITORS PYR; PYR20 AND WITH NADP, SUBUNIT, CHARACTERIZATION OF PYRIMETHAMINE-RESISTANT VARIANT ASN-117, CATALYTIC ACTIVITY.

Entry informationi

Entry nameiDRTS_PLAVI
AccessioniPrimary (citable) accession number: O02604
Secondary accession number(s): O15873
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: May 14, 2014
This is version 86 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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