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P00381

- DYR_LACCA

UniProt

P00381 - DYR_LACCA

Protein

Dihydrofolate reductase

Gene

folA

Organism
Lactobacillus casei
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

    Catalytic activityi

    5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei22 – 221May be important for enzyme function
    Binding sitei27 – 271Methotrexate1 Publication
    Binding sitei27 – 271Substrate
    Binding sitei32 – 321Methotrexate1 Publication
    Binding sitei32 – 321Substrate
    Binding sitei58 – 581Methotrexate1 Publication
    Binding sitei58 – 581Substrate
    Binding sitei80 – 801NADP; via amide nitrogen1 Publication
    Binding sitei117 – 1171Substrate

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi6 – 72NADP1 Publication
    Nucleotide bindingi14 – 196NADP1 Publication
    Nucleotide bindingi43 – 464NADP1 Publication
    Nucleotide bindingi63 – 664NADP1 Publication
    Nucleotide bindingi98 – 1036NADP1 Publication

    GO - Molecular functioni

    1. dihydrofolate reductase activity Source: UniProtKB-EC
    2. NADP binding Source: InterPro

    GO - Biological processi

    1. glycine biosynthetic process Source: InterPro
    2. nucleotide biosynthetic process Source: InterPro
    3. one-carbon metabolic process Source: UniProtKB-KW
    4. response to antibiotic Source: UniProtKB-KW
    5. response to methotrexate Source: UniProtKB-KW
    6. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Antibiotic resistance, Methotrexate resistance, One-carbon metabolism

    Keywords - Ligandi

    NADP

    Enzyme and pathway databases

    SABIO-RKP00381.
    UniPathwayiUPA00077; UER00158.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Dihydrofolate reductase (EC:1.5.1.3)
    Gene namesi
    Name:folA
    Synonyms:dhfR
    OrganismiLactobacillus casei
    Taxonomic identifieri1582 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesLactobacillaceaeLactobacillus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 163162Dihydrofolate reductasePRO_0000186393Add
    BLAST

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Structurei

    Secondary structure

    1
    163
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi3 – 86
    Turni10 – 123
    Beta strandi13 – 164
    Helixi25 – 339
    Turni34 – 374
    Beta strandi38 – 436
    Helixi44 – 496
    Beta strandi50 – 545
    Beta strandi58 – 636
    Beta strandi67 – 693
    Beta strandi74 – 796
    Helixi80 – 8910
    Beta strandi91 – 933
    Beta strandi95 – 973
    Helixi101 – 1066
    Helixi108 – 1103
    Beta strandi113 – 1219
    Beta strandi126 – 1283
    Helixi134 – 1363
    Beta strandi137 – 1459
    Helixi150 – 1523
    Beta strandi154 – 1618

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AO8NMR-A2-163[»]
    1BZFNMR-A2-163[»]
    1DISNMR-A2-163[»]
    1DIUNMR-A2-163[»]
    1LUDNMR-A2-163[»]
    2HM9NMR-A2-163[»]
    2HQPNMR-A2-163[»]
    2L28NMR-A2-163[»]
    2LF1NMR-A2-163[»]
    3DFRX-ray1.70A2-163[»]
    ProteinModelPortaliP00381.
    SMRiP00381. Positions 2-163.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP00381.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 161160DHFRPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni5 – 73Substrate binding

    Sequence similaritiesi

    Belongs to the dihydrofolate reductase family.Curated
    Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

    Family and domain databases

    Gene3Di3.40.430.10. 1 hit.
    InterProiIPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR017925. DHFR_CS.
    IPR001796. DHFR_dom.
    [Graphical view]
    PfamiPF00186. DHFR_1. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000194. DHFR. 1 hit.
    PRINTSiPR00070. DHFR.
    SUPFAMiSSF53597. SSF53597. 1 hit.
    PROSITEiPS00075. DHFR_1. 1 hit.
    PS51330. DHFR_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P00381-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTAFLWAQDR DGLIGKDGHL PWHLPDDLHY FRAQTVGKIM VVGRRTYESF    50
    PKRPLPERTN VVLTHQEDYQ AQGAVVVHDV AAVFAYAKQH PDQELVIAGG 100
    AQIFTAFKDD VDTLLVTRLA GSFEGDTKMI PLNWDDFTKV SSRTVEDTNP 150
    ALTHTYEVWQ KKA 163
    Length:163
    Mass (Da):18,439
    Last modified:January 23, 2007 - v3
    Checksum:i1E4B556ED7A750D1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti9 – 91D → N AA sequence (PubMed:98527)Curated
    Sequence conflicti91 – 911P → L AA sequence (PubMed:98527)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M10922 Genomic DNA. Translation: AAA25237.1.
    PIRiA24036. RDLBD.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M10922 Genomic DNA. Translation: AAA25237.1 .
    PIRi A24036. RDLBD.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AO8 NMR - A 2-163 [» ]
    1BZF NMR - A 2-163 [» ]
    1DIS NMR - A 2-163 [» ]
    1DIU NMR - A 2-163 [» ]
    1LUD NMR - A 2-163 [» ]
    2HM9 NMR - A 2-163 [» ]
    2HQP NMR - A 2-163 [» ]
    2L28 NMR - A 2-163 [» ]
    2LF1 NMR - A 2-163 [» ]
    3DFR X-ray 1.70 A 2-163 [» ]
    ProteinModelPortali P00381.
    SMRi P00381. Positions 2-163.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P00381.
    ChEMBLi CHEMBL2902.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Enzyme and pathway databases

    UniPathwayi UPA00077 ; UER00158 .
    SABIO-RK P00381.

    Miscellaneous databases

    EvolutionaryTracei P00381.

    Family and domain databases

    Gene3Di 3.40.430.10. 1 hit.
    InterProi IPR012259. DHFR.
    IPR024072. DHFR-like_dom.
    IPR017925. DHFR_CS.
    IPR001796. DHFR_dom.
    [Graphical view ]
    Pfami PF00186. DHFR_1. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000194. DHFR. 1 hit.
    PRINTSi PR00070. DHFR.
    SUPFAMi SSF53597. SSF53597. 1 hit.
    PROSITEi PS00075. DHFR_1. 1 hit.
    PS51330. DHFR_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Nucleotide sequence of the dihydrofolate reductase gene of methotrexate-resistant Lactobacillus casei."
      Andrews J., Clore G.M., Davies R.W., Gronenborn A.M., Gronenborn B., Kalderon D., Papadopoulos P.C., Schaefer S., Sims P.F.G., Stancombe R.
      Gene 35:217-222(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Dihydrofolate reductase from amethopterin-resistant Lactobacillus casei. Sequences of the cyanogen bromide peptides and complete sequences of the enzyme."
      Freisheim J.H., Bitar K.G., Reddy A.V., Blankenship D.T.
      J. Biol. Chem. 253:6437-6444(1978) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-163.
    3. "Dihydrofolate reductase from Lactobacillus casei: N-terminal sequence and comparison with the substrate binding region of other reductases."
      Batley K.E., Morris H.R.
      Biochem. Biophys. Res. Commun. 75:1010-1014(1977) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-52.
    4. "Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7-A resolution. II. Environment of bound NADPH and implications for catalysis."
      Filman D.J., Bolin J.T., Matthews D.A., Kraut J.
      J. Biol. Chem. 257:13663-13672(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH NADPH AND METHOTREXATE.
    5. "Dihydrofolate reductase: sequential resonance assignments using 2D and 3D NMR and secondary structure determination in solution."
      Carr M.D., Birdsall B., Frenkiel T.A., Bauer C.J., Jimenez-Barbero J., Polshakov V.I., McCormick J.E., Roberts G.C.K., Feeney J.
      Biochemistry 30:6330-6341(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.
    6. "Solution structure of a brodimoprim analogue in its complex with Lactobacillus casei dihydrofolate reductase."
      Morgan W.D., Birdsall B., Polshakov V.I., Sali D., Kompis I., Feeney J.
      Biochemistry 34:11690-11702(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.
    7. "The solution structure of the complex of Lactobacillus casei dihydrofolate reductase with methotrexate."
      Gargaro A.R., Soteriou A., Frenkiel T.A., Bauer C.J., Birdsall B., Polshakov V.I., Barsukov I.L., Roberts G.C.K., Feeney J.
      J. Mol. Biol. 277:119-134(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.
    8. "Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate."
      Polshakov V.I., Birdsall B., Frenkiel T.A., Gargaro A.R., Feeney J.
      Protein Sci. 8:467-481(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR.

    Entry informationi

    Entry nameiDYR_LACCA
    AccessioniPrimary (citable) accession number: P00381
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 102 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    This bacterial strain is resistant to the folic acid analog methotrexate (amethopterin).

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    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