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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.

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 – 3601dUMPBy similarity
Active sitei505 – 5051By similarity
Binding sitei506 – 5061dUMPBy similarity
Binding sitei536 – 5361dUMPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi38 – 447NADP
Nucleotide bindingi115 – 1173NADP
Nucleotide bindingi137 – 1393NADP
Nucleotide bindingi174 – 1818NADP
Nucleotide bindingi524 – 5285dUMPBy similarity
Nucleotide bindingi566 – 5683dUMPBy 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 synthasePRO_0000186351Add
BLAST

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

1
623
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 74Combined sources
Beta strandi10 – 1910Combined sources
Beta strandi23 – 264Combined sources
Beta strandi38 – 414Combined sources
Beta strandi46 – 483Combined sources
Helixi51 – 6212Combined sources
Helixi66 – 683Combined sources
Helixi69 – 8315Combined sources
Beta strandi109 – 1146Combined sources
Helixi115 – 1195Combined sources
Helixi123 – 1253Combined sources
Beta strandi131 – 1366Combined sources
Turni142 – 1443Combined sources
Beta strandi150 – 1534Combined sources
Helixi155 – 1639Combined sources
Beta strandi170 – 1745Combined sources
Helixi176 – 1849Combined sources
Beta strandi189 – 20012Combined sources
Beta strandi203 – 2053Combined sources
Helixi211 – 2133Combined sources
Beta strandi214 – 2196Combined sources
Beta strandi223 – 2253Combined sources
Beta strandi228 – 23710Combined sources

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiO02604.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 237229DHFRAdd
BLAST
Repeati88 – 9141
Repeati94 – 9742
Repeati100 – 10343

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni13 – 142Substrate binding
Regioni88 – 103163 X 4 AA repeats of G-G-D-NAdd
BLAST
Regioni337 – 623287Thymidylate synthaseAdd
BLAST

Domaini

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

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

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

        10         20         30         40         50
MEDLSDVFDI YAICACCKVA PTSEGTKNEP FSPRTFRGLG NKGTLPWKCN
60 70 80 90 100
SVDMKYFSSV TTYVDESKYE KLKWKRERYL RMEASQGGGD NTSGGDNTHG
110 120 130 140 150
GDNADKLQNV VVMGRSSWES IPKQYKPLPN RINVVLSKTL TKEDVKEKVF
160 170 180 190 200
IIDSIDDLLL LLKKLKYYKC FIIGGAQVYR ECLSRNLIKQ IYFTRINGAY
210 220 230 240 250
PCDVFFPEFD ESQFRVTSVS EVYNSKGTTL DFLVYSKVGG GVDGGASNGS
260 270 280 290 300
TATALRRTAM RSTAMRRNVA PRTAAPPMGP HSRANGERAP PRARARRTTP
310 320 330 340 350
RQRKTTSCTS ALTTKWGRKT RSTCKILKFT TASRLMQHPE YQYLGIIYDI
360 370 380 390 400
IMNGNKQGDR TGVGVMSNFG YMMKFNLSEY FPLLTTKKLF LRGIIEELLW
410 420 430 440 450
FIRGETNGNT LLNKNVRIWE ANGTREFLDN RKLFHREVND LGPIYGFQWR
460 470 480 490 500
HFGAEYTNMH DNYEDKGVDQ LKNVIHLIKN EPTSRRIILC AWNVKDLDQM
510 520 530 540 550
ALPPCHILCQ FYVFDGKLSC IMYQRSCDLG LGVPFNIASY SIFTHMIAQV
560 570 580 590 600
CNLQPAQFIH ILGNAHVYNN HVDSLKVQLN RIPYPFPTLK LNPEVKNIED
610 620
FTISDFTIEN YVHHDKITME MAA
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.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98123 Genomic DNA. Translation: CAA66805.1.
PIRiJC6568.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X98123 Genomic DNA. Translation: CAA66805.1 .
PIRi JC6568.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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: October 29, 2014
This is version 88 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