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P00381

- DYR_LACCA

UniProt

P00381 - DYR_LACCA

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Protein

Dihydrofolate reductase

Gene

folA

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

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
Complete GO annotation...

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

        10         20         30         40         50
MTAFLWAQDR DGLIGKDGHL PWHLPDDLHY FRAQTVGKIM VVGRRTYESF
60 70 80 90 100
PKRPLPERTN VVLTHQEDYQ AQGAVVVHDV AAVFAYAKQH PDQELVIAGG
110 120 130 140 150
AQIFTAFKDD VDTLLVTRLA GSFEGDTKMI PLNWDDFTKV SSRTVEDTNP
160
ALTHTYEVWQ KKA
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