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O02604

- DRTS_PLAVI

UniProt

O02604 - DRTS_PLAVI

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
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    • History
      Entry version 87 (01 Oct 2014)
      Sequence version 2 (30 May 2000)
      Previous versions | rss
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    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

    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 – 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.
    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

    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.

    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: October 1, 2014
    This is version 87 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